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And I'd like to thank the organisers
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the inviting me to speak with you today
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this is just a a fantastic symposium on
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very interested and excited to to hear
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all of the tools. Um what I want to do
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today is really to to about really
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environment Somehow the early
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empowerment shapes the developing brain
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I'm going to run through says of of
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concepts and and and areas I go through
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the to to die by I'm going to use
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illustrations from my lap and from from
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other labs to illustrate the concepts
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that I'm going to be talking to you
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about so I really want to start by
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first we'll talking about the concept
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of a like programming us a little bit
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about Ryan in your and can develop
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because that's critical if we don't
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understand how the environment
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influences developing. And then don't
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say something about how clean record
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colours in the developing brain program
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have the ability to programme function
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but in terms of structure that idea and
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the near in different function. I want
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to then spent some time talking about
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the mechanisms and lastly some of the
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work that we've been doing recently
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which is is around the impact of
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unemployment in the trends generation
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transmission of the sex and that with
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finding now. So the environment during
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early life. Uh establishes life on
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trajectories to how disease Lenin
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capability and social function we've
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known that for many years. Um really it
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was some of the work of David pocket
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that brought it back to the forefront
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showing the small babies have a high
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risk of cardiovascular disease. And he
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went on to show many other associations
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as I'm sure many of you know but that
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really reinvigorated to fill which had
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been not I've been around since the
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thirties forties fifties linking early
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environment too late onset disease in
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late onset social change. But that is
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really important studies bring into the
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human my these feel really go through a
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renaissance and there's been huge
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interest in the larger media around
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this time of actually run several
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issues and how the invite early
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environment in this is the rest of your
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life. Well it's not that much of by
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john really because we know that a lot
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happens in the first years of life if
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one considers moving from a two cell
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embryo through to a new won't tell the
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enormous changes that have occurred
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within that organisation as it's
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developed it's not prize in the the
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environment can happen in time when we
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think about the developing Brian and
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I'm sorry Michael I'm using the wrong
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number I know not change this tidy nine
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rather than a hundred billion neurons.
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But the developing brain but the right
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now but essentially has the majority of
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neurons it's ever gonna have a hundred
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billion neurons right to nine billion
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neurons by you talk to each other. So
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there are more than sixty trillion sign
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axes within that Brian what happens in
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the three line and all of this is
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talking during prenatal period is that
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there is a massive overproduction of
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neurons there's then ordered I is is
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about fifty percent of the neurons of
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the one actually die and there's a huge
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amount of synaptic pruning the cousin
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like gestation. in the human and then
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only live in early post like And then
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it's plus like like a lot of writing
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about because and you get the formation
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of the clear structures and modulation
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of the bright and as many of you know
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to be at the the C sure Brian inhuman
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as a cheap I Song so there's an
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enormous amount that happens during
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early life with theirs select brain
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development what we're very interested
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then is how these early influences have
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really not environment can influence
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long term outcome. And here I'm
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summarising the work of several groups
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and thousands of publications showing
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but not online sliding stress hormones
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drugs central insufficiency on the
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nutrition during pregnancy more
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recently the importance of maternal
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he's two and maternal yeah have a huge
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impact. on like one health they have
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about problems associated with
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hypertension insulin resistance
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diabetes obesity student council. So
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more peripheral effects on the left
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hand side but we also know the right
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significant effects within the
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developing brain around learning
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abilities links to attention deficit
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hyperactivity disorder depression and
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self regulation but what's really
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important is understanding what links
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there limp on this is what my life So
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I'm not interested in what links the
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only environment to change them on how
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how long do these effects last and one
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point that I also I mean from the slide
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is what can we do to prevent or reverse
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the effects of these office early
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environments. So less on the few
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minutes talking about brain and your in
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the current development we know
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actually quite a lot about the
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developing Brian and on my group and
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and others have spent several years on
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stand development of certain systems
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within the developing brain we've been
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particularly interested in the
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hypothalamus pituitary adrenal axis and
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mean I I access is well developed in
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the features in this is just a an
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outline of this a schematic of the axis
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we have the hippocampus up here that
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we've already seen lots of pictures of
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later in the by the hippocampus forming
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part of the limbic system is important
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in setting the tone of the carpentry
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clean you place in the hypothalamus
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which produces yeah right and vice
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president which then draw if the
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anterior feature three to synthesise
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and secrete ice tea age ultimately
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produce courses all the system is
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tightly regulated court chords are very
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important and very effective in setting
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her mistress is within an individual
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but I can be quite damaging if the left
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the high levels for any period of time
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and so there is I very well developed
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feedback system where there's a number
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of people cortical receptive the
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mineral aboard quadriceps and
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hippocampus. And cold quadriceps as in
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the power ventricular nucleus and the
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and to protect three so these good code
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chords can feedback. And down regulate
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and the the axis in a negative
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feedback. And this we know is well
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developed in the features we know that
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the features if the features is
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stressed this system can be activated.
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We know that you could could feedback
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as an operation. But something very
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interesting happens as foetus
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approaches to this system goes in the
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hard drive on this on the right hand so
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it aside is I type from abby fountains
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peeping Cambridge Shari the increases
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the in fiddle plastic also
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concentrations in the law harder
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gestation in several maniacally in
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space. So you can see yeah but over the
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last few weeks of gestation. They
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concentrations of speaking plasma
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courts will increase what I told you is
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that that was all regulated nice I told
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you the code code feedback is in place
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and developing a fiddle item to treat
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relaxes but something happens to allow
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the access to going to not drive and
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that's something that would be very
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interested in and continue to be
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interesting is what allows this to
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happen we know that there is a chance
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of maternal holds all across the
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placenta the features but together with
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maternal unspeakable counsel this this
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big increase I doesn't shut down the
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axis in like two station why this
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searching important research is really
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important because court chords are
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critical in preparing the features to
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the and then right that's very
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important in development of the fickle
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along to create a line that we work in
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is is being fluid so that will now in
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and and environment. And so that the
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record such essentially switches many
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systems take the the line the kidney
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and also the brine into and the and I
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write we know that the bright and the
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like in like gestation the fickle brain
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is has high levels of record quadriceps
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within it this is actually I like
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gestation a guinea pig right guinea pig
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gives birth to very mature and your
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anatomically immature offspring. And
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here we have a cross section showing
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the hippocampus in the daytime jars and
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the power ventricular nucleus
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structures like just introduce to you
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as well as they make a lot and you can
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see very high levels of people go to
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set up in these brain structures in
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legislation we know the sign is true in
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humans. So the brain is very receptive
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to record codes and very receptive to
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that group called good search and what
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went I mean what others have shown is
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that difficult chords really are remote
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switch in the features and by our
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critical mass to switch in the
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developing brain and I'm going to come
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back like from the Mike to to show you
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the data but we know that this which is
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important the level of gene
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transcription and the level of a
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genetic modification necessary I will
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come back to show you the data to about
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that later on so what about record
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colloids and programming. Well my lab
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has been very interested in how the
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prenatal environment particularly
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maternal adversity. And specifically
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look cool chords probably in fact on
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the developing brain to affect limbic
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system development to affect the
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hypothalamus and two or three and to
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lead to changes in stress and the
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chronology and the behaviour and in the
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reason for the red arrow between
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behaviour and learning. And stress and
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acknowledges we know that you go to it
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a very important in setting activity
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within the brain very important in
00:11:10
about anybody views and also learning
00:11:13
we also know that long chance long term
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changes in stress endocrinology can
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lead to disease susceptibility long
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term changes in court so concentrations
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can have you looked at the facts how
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certainly implicated in these I again
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I'll come back to that a little later
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in my presentation. So would you go
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that to corporate so it is really
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important like gestation. But if the
00:11:38
features is a lot of pixel the mother
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all stressed then you could chords can
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go up in the theatres before that final
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us because we're very interested in is
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the consequence of I think cool chord
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search earlier then it's meant to be on
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the developing brain we know that
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maternal stress anxiety depression
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abuse and violence lead to increases in
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maternal court so we know that there is
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a barrier between the mother and the
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fixed in time at a local so
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concentrations about twenty times
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harder now in the features and that's
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very important. But if you increase
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maternal also if maternal courts always
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increases as a result of stress we do
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know that there is an increase in
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federal court so concentration the
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features as I told you can respond to
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stress itself and we know that stress
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is like fibreglass Syria five proxy in
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infection can increase console
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concentrations in the features we also
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know that syntactically gold chords
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which are given to pregnant women will
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move across the placenta and and the
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features and and to the developing
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brain and this is actually a very
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important clinical issue because
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approximate ten percent of pregnant
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women a diagnosis with preterm labour.
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And the majority of those women and
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well well well received syntactically
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good good treatment reason I receive
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syntactic look good good treatment is
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too much of the people on remember that
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so a onto the end of gestation with a
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features is only for that matter search
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it's Liza not gonna work very
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effectively person likely someone
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getting a syntactically called quite a
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treatment to the mother you accelerate
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fiddle on development so that features
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but I think along functions much better
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off the path and in fact we know that
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that record good treatment is very
00:13:34
important in reducing respiratory
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distress syndrome in new bones it's a
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very very effective treatment. But
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we've been very interested in
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understanding whether there is a cost
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of such a treatment in the developing
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brain which we know is listening to
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good good concentrations in the
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features. So what do we know what we
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not in and it's American studies and
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human studies that exposure was
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developing brain. So high levels of
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cord going before that normally exposed
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to clean hold word can have effects on
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brain structures can have a pet on
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behaviours can have effects on your
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right near century function. We just
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published recently a follow up in a
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chart shine entropy code court
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exposures impact new sensory function
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children of years of age. Um have
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impact on your function and currently
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metabolic function what I'm going to do
00:14:34
in the next few slides is to give you
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some illustrations of that from what
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happened from from other labs the first
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comes from illicit Davis and colonies
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UC davis. And well basically it is by a
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lot of the impact of giving only court
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court side I think of course in this
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case of course quite but they look like
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using a Mariah children who was six to
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ten user might these children had to
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see it as is all the mothers receives a
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syntactically go to treatment leprosy
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one single course of code goes and
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these models of actually now coming to
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turn to look a thumb. So premature to
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was factored out of this particular
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follow up something that's another
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important point. But around thirty
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percent of women who are diagnosed with
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suspect or suspects of of having
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preterm birth and receive syntactically
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good good around thirty percent of
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those women go want you but a long time
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and that's because actually diagnosing
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freedom but this is quite difficult. So
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in this study what Lisa like this and
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and calling showed was that when you
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look in the anterior singular cortex
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that was the thinning of the cortex in
00:15:52
the anterior singular cortex we know
00:15:55
that a feeling of the cortex at this
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point is associated with an increase in
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affective disorders and this was really
00:16:02
the first date so I'm anatomical study
00:16:05
showing that I can good could could
00:16:07
have a long term outcome now this is a
00:16:09
relatively small study. And it is a
00:16:12
retrospective study and so one has to
00:16:14
consider the limitations of that type
00:16:16
of approach there's also be some very
00:16:22
recent studies from attendants guys
00:16:25
found very interesting in Germany doing
00:16:29
a follow up study of protruded renal
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function in children that six to ten
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years of age following pretty good
00:16:35
corporate exposure and in this study
00:16:40
not as this was done in children of
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modesty was hospitalised during
00:16:47
pregnancy which is the circles I was
00:16:50
hospitalised in pregnancy and given
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record codes because of suspected
00:16:54
preach number. But all of these women
00:16:56
to give the but give but the normal one
00:17:00
of the women and starting another group
00:17:01
of women hot like during pregnancy but
00:17:05
did not receive will go towards the end
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of the group were controls to wear
00:17:09
matched controls it will not impossible
00:17:11
during pregnancy. And a six to ten
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years of age these children are exposed
00:17:17
the true a child but to trust us test
00:17:20
train a stress test which is the gold
00:17:22
standard of assessing project original
00:17:25
function in humans and when I did this
00:17:27
test in these six to ten year old
00:17:29
children that is his mother ceasing
00:17:31
that'd be cool chord showed a bigger a
00:17:34
great a responsible right supercharger
00:17:36
Adrian response to the tree a stress
00:17:39
test interestingly I thought was most
00:17:42
prominent in goes next prominent
00:17:44
invoiced. So when you using a model of
00:17:49
an interested in understanding the
00:17:51
mechanisms and the routes by which
00:17:54
prenatal group record might be
00:17:55
affecting these structures and I'm
00:17:58
going to just show you a very small
00:17:59
amount of data I mean that we generated
00:18:03
matlab with we published options area
00:18:06
over the last several years I'm just
00:18:08
going to illustrate with some examples.
00:18:10
So in this model we use the guinea pig
00:18:14
as a model because the guinea pig
00:18:15
actually shows in your development
00:18:17
contracts pattern which is not close to
00:18:19
the human then that's a nice maximises
00:18:22
you know give but the very racial young
00:18:25
and a lot of crime development
00:18:27
important brain development that goes
00:18:29
on in the human brain actually have
00:18:31
most likely maximise. So by using a
00:18:34
guinea pig model we're using a mobile
00:18:35
where development profiles are quite
00:18:38
similar to the human it has a much
00:18:41
longer gestation than mice now I have
00:18:44
ascended I gestation. So we can really
00:18:46
focus in a specific time points to look
00:18:48
at the impact of difficult words in
00:18:50
this case we gave three repeat cost of
00:18:53
course what we're able to then look
00:18:56
acutely and I'll show you some of that
00:18:58
I'd like to aware able to look
00:19:00
longitudinally in in the first
00:19:03
generation indeed across multiple
00:19:05
generations when we look at and
00:19:08
approved function I'm I guess I'm just
00:19:10
gonna show you two examples. So this is
00:19:13
an example where we are pretty nightly
00:19:16
expose to the fix is to syntactically
00:19:20
record going with a look at these
00:19:22
examines one that you can also buy
00:19:24
twenty four and a was seated human in
00:19:29
the offspring his not see syntactically
00:19:32
look good does the increase in that
00:19:34
church journals problems when we put
00:19:36
them into my comfortable environment
00:19:38
and significantly elevated over the the
00:19:43
controls again we or bigger effect in
00:19:47
females use one mile so we are saying
00:19:49
sex specificity of disaffected printed
00:19:52
who could we also the behaviours and
00:19:55
showing the way we put these young
00:19:57
animals into an open filled environment
00:19:59
if the mothers got syntactically
00:20:02
recorded voice they are hyperactive in
00:20:05
the open field environment as young
00:20:08
animals but again this is only seen in
00:20:12
females with this particular model we
00:20:14
don't see the hyperactivity Miles well
00:20:16
you know in the brain to see what's
00:20:18
actually going on with the whole series
00:20:21
of systems within the brine one of
00:20:23
things that consistently part not
00:20:25
actually is the hip accountable and the
00:20:28
air receptor. And in these animals
00:20:30
where they're hyperactive in the post
00:20:33
like a files following pretty nice
00:20:35
corporate exposure interestingly we see
00:20:38
a reduction in the panel once song you
00:20:41
subunit at the end N the I receptor
00:20:43
again effect is in females only it's
00:20:47
not seen in Miles interestingly with
00:20:50
all these studies looking at long some
00:20:52
potentially asian in your hands and
00:20:54
change no as we might expect this
00:20:57
alteration in and then the receptors an
00:20:59
alteration in long term potential
00:21:01
fashion associated prenatal exposure.
00:21:04
So the take home message from this part
00:21:09
of my two is that the thing like yeah
00:21:12
this is well developed and like just
00:21:14
station. But that is funny programmable
00:21:16
we know this from several studies that
00:21:20
is possible to programme should read
00:21:22
relapses by manipulating an environment
00:21:24
that's not a question we can manipulate
00:21:27
and and get different outcomes with
00:21:29
respect to children function twice as
00:21:31
important. It's important because the
00:21:33
project original system courses
00:21:35
optically is very important in
00:21:37
regulating metabolism growth repair
00:21:39
reproduction sensibly resource
00:21:42
allocation within the body as I
00:21:44
mentioned earlier very important in
00:21:47
behaviour and learning and we know that
00:21:51
record was very active within the and
00:21:53
within the transcripts on that and I'm
00:21:58
not quite as that expression of more
00:22:01
than ten percent of the G nine and we
00:22:03
know that in many chronic diseases
00:22:06
there's this regulation the children of
00:22:08
function in in many cases hyperactivity
00:22:11
increased code so concentrations
00:22:14
associated with diseases like in some
00:22:17
distance probabilities. So what about
00:22:21
mechanisms how is it that early
00:22:24
exposure to glue records if all the
00:22:26
time and is that national hold word
00:22:28
such how is it that good could go to
00:22:32
have and then well there are probably
00:22:35
and we know the redirect actions. So
00:22:38
good chords affect structure more and
00:22:41
we know that record record or practical
00:22:44
for several aspects of your development
00:22:46
near genesis I popped else's so naps
00:22:49
formation sign not pretty all things
00:22:52
now in in brain development oh you put
00:22:56
words are important to court court is
00:22:59
bad too much political good is bad this
00:23:02
set right it's quick school and that's
00:23:04
why the features I think you could go
00:23:06
to trial. So tightly regular. So good
00:23:10
corporate Reno can impact structural
00:23:12
development. That's been shown by and
00:23:15
many studies in primates and also in
00:23:18
lower animals there are indirect
00:23:20
effects because we have a good record
00:23:22
could impact the development of all the
00:23:24
systems of thought says the level
00:23:27
placenta we're not far much critical in
00:23:29
brain development we know the labour
00:23:31
produces C courses start pointing
00:23:33
popular and record was gonna fit that
00:23:36
during thinking about the placenta is
00:23:39
very important in protecting the
00:23:40
features from factors in internal
00:23:43
circulation produces enzymes like
00:23:45
eleven may try to stick to which allow
00:23:47
the criterion of course so between the
00:23:49
mountains features we know that go with
00:23:51
the fact that so several indirect ways
00:23:53
in which blew good good might be
00:23:55
affecting the features. And then of
00:23:57
course there's the possibility that the
00:24:00
court codes are in fact having direct a
00:24:02
genetic effects we know that several of
00:24:04
the duration of important regulating
00:24:06
children function or in fact at
00:24:09
genetically modulated or not and that's
00:24:11
O where we spent a lot of innocent
00:24:13
folks wanna spend the next part to
00:24:15
talking to you about that would be very
00:24:18
interested then in how early supposed
00:24:22
to go to court affects the development
00:24:25
of the LPG no we we take really
00:24:29
interested in the hippocampus the hard
00:24:31
times in church and I'm just going to
00:24:34
talk to you briefly about hippocampus
00:24:35
today would be interested in at the end
00:24:40
I not location micron I am a sec like
00:24:42
some but I'm gonna just confine other
00:24:45
dated I'm gonna show you to die to do
00:24:48
and I method location. So we did some
00:24:50
very simple experiments nations done in
00:24:53
collaboration which is the Mcgill
00:24:57
university what we did is we simply
00:25:02
really really people account like Gina
00:25:04
before and after an attribute put would
00:25:07
search and we said how gene expression
00:25:11
change how does deny my collection
00:25:13
change first thing is when we look
00:25:16
before no clue what search comparing
00:25:18
fifty two to sixty five we see that
00:25:21
there is profound changes in the
00:25:24
transcription change says a change in
00:25:26
the transcription around eleven hundred
00:25:29
genes the majority the jeans there
00:25:31
isn't increasing expression okay when
00:25:37
we look using a genome wide approach
00:25:40
using and he did followed by a rice. We
00:25:44
look at my relation across the apogee
00:25:48
nine at these two time points we see
00:25:51
that as gestation progresses from by
00:25:54
fifty two two by sixty five or there an
00:25:57
increase in mechanisation in some jeans
00:26:00
predominantly we've got a team
00:26:02
escalation process occur the green here
00:26:06
in the case team appellation each of
00:26:08
these lines here represents the
00:26:10
hippocampus all I features from
00:26:13
independent models by fifty two and a
00:26:17
sixty five so that surgeon like just
00:26:20
station. And the developmental changes
00:26:23
between fifty to sixty five clearly
00:26:26
indicate demon license or what's
00:26:28
happening man is that cortical it's we
00:26:31
think it coming in result in a team
00:26:34
appellation Elan transcription factors
00:26:36
all two point coming and the genes to
00:26:38
be switched on so we think now we
00:26:41
understand then at least how there's a
00:26:42
massive R again a regulation of gene
00:26:45
expression legislation obviously a lot
00:26:48
happening between like fifty two and a
00:26:50
sixty five it's not just political
00:26:52
causes a lot of other developmental
00:26:53
processes going on. So we can describe
00:26:55
all of this to clear called good but
00:26:57
it's a nice association. So the next
00:27:00
question then is what happens if we see
00:27:02
like the code word search by giving
00:27:05
look good words. So here we guy we got
00:27:12
a a report quite syntactical wants to
00:27:15
model. And I fourteen day fifty we
00:27:18
looked at this is available for the
00:27:21
natural to record could search. We are
00:27:24
slight questions we looked at gene
00:27:25
expression and and I'm appellation
00:27:28
within the hippocampus what we saw race
00:27:31
we saw an increase in expressive around
00:27:33
eleven hundred genes with this early
00:27:35
exposure to cold calling. And when we
00:27:42
look to the D and I met relation
00:27:43
profile with so exactly the same
00:27:46
follows we see following the the that
00:27:50
so called good search. So this goddess
00:27:52
strikes article why would just
00:27:54
simulated the record quite search like
00:27:57
gestation people also it by giving
00:28:00
record got well of course as in all
00:28:04
experiments it's never a simple as you
00:28:06
thing. And each of these lines
00:28:09
represents a different G so we have
00:28:12
cost all the train isn't allowed to go
00:28:15
back. And look at each of the jeans and
00:28:19
tell us which genes were affected how
00:28:21
they're affected and whether they would
00:28:24
sign but time points. And in fact what
00:28:27
emerged was quite an interesting story
00:28:29
that when we looked at the map
00:28:31
collection profile with a change in
00:28:34
that collection protocol of two hundred
00:28:35
fifty seven and promoters between fifty
00:28:39
to sixty five hundred twenty three
00:28:42
between fifty to a before all without a
00:28:47
people Gordon and those at the been
00:28:49
cool could expose remember that next
00:28:52
election profiles look really similar
00:28:54
but in fact the different genes only
00:28:57
fourteen of the metal a simple force
00:29:00
correspond to the to the same jeans. So
00:29:03
this sounds really I think can be
00:29:06
looked at in two ways perhaps. It's the
00:29:08
time of exposure this critical if you
00:29:11
expose the prime to a little place
00:29:13
called quite in fact what you do is you
00:29:16
all through completely different genes
00:29:18
that or alternatively colours which is
00:29:22
the endogenous blue record quite in
00:29:24
guinea pigs and in humans is different
00:29:27
some syntactically court chords because
00:29:29
and I quote all points to buy them in a
00:29:32
local produce that and blue good good
00:29:34
perception of the campus where a
00:29:36
syntactically good good spine
00:29:38
specifically to the clue to go to
00:29:40
stepped up. So that might be I found a
00:29:43
logical affect a carnal and these are
00:29:46
very important issues that we need to
00:29:47
ones that oh what I wanted to because
00:29:51
we have everything energy gym bags
00:29:54
resolution we can go ahead and we can
00:29:57
use GR chip to say exactly where that
00:29:59
will report good receptors pointing
00:30:02
today and I we can look at my
00:30:03
collection around by binding site and
00:30:06
we can look at how that's affecting
00:30:07
transcription we we do that quite
00:30:09
regularly we can also do longitudinal
00:30:12
analysis what actually is data from
00:30:14
fixes the next question is what happens
00:30:18
to in juveniles what happens in young
00:30:20
adults what happens in ageing I don't
00:30:22
what happens across multiple
00:30:23
generations is this a genetic signature
00:30:27
does it remind or does it change with
00:30:30
development. And I think the likelihood
00:30:32
is that the to check that the latter is
00:30:35
the case that court quite have a big
00:30:38
impact on developing apogee nine but I
00:30:40
essentially then also the trajectory of
00:30:43
I gene and as development carries on
00:30:45
another individual goes through life.
00:30:48
So radically court point impact the
00:30:50
developing averaging on this is
00:30:51
something that we've got I've become
00:30:53
very interested in I already alluded to
00:30:57
the fact that report points modify
00:31:00
other systems we know the modification
00:31:02
of part of polymers certainly would
00:31:05
impact potentially the people get the
00:31:08
camp leveraging know of course points
00:31:10
might alter the transporter percent so
00:31:13
maybe I'll do it as across the placenta
00:31:16
the court quite directly interact with
00:31:19
the GRA to influence not collection
00:31:21
which are not very clearly the court
00:31:23
records all also also the regulation of
00:31:27
a number of critical and genetic
00:31:29
regulated genes like the NMT and then
00:31:32
the NBD to published work showing that
00:31:35
that in the the case we also know that
00:31:37
you put chords can modify the I'm not
00:31:41
finding cycle patients for example with
00:31:44
cushions syndrome have like a
00:31:46
pharmacist anaemia. We know that the
00:31:49
court chords longterm exposed to
00:31:51
likelihood boards can affect them
00:31:53
authority cycle we also know now the
00:31:55
clue good good seem to be affecting
00:31:57
micro I so the remote wise ways in
00:32:00
which blew go what's gonna impact with
00:32:02
about an IPG non oh but if we
00:32:05
understand the mechanisms the next
00:32:07
question we have is can we can wait a
00:32:10
create interventions to protect or
00:32:12
reverse the effects of well it's very
00:32:16
good good at all to the go got exposure
00:32:19
in the developing is really beneficial
00:32:21
in the developing on but is ending we
00:32:23
can do to protect they facts within
00:32:25
central nervous system and I'm thinking
00:32:29
about interventions that have been a
00:32:31
number of studies that have used
00:32:33
interventions to reverse adverse ugly
00:32:36
environments we know from the work of
00:32:38
an problem and markets is group in a
00:32:41
Southampton that photographic
00:32:43
supplements and protect against for our
00:32:48
hands associated internal a diet that
00:32:51
time with all alternate arts can
00:32:52
protect against the BBCT in offspring
00:32:55
that are susceptible to I've recently
00:32:57
that the wonderful working more to land
00:32:59
down in texas. But climbing although
00:33:02
the clients can improve not near a
00:33:04
cognitive homes in it but the but on
00:33:08
the other hand also sunshine the
00:33:10
effects on a small so this is certainly
00:33:13
a very controversial area. And the what
00:33:17
of the more she's a flat and any "'em"
00:33:20
we've learned my meaning shine that and
00:33:23
you can inject the finding into the
00:33:25
brian's about all rat that were exposed
00:33:27
to for maternal yeah and you can
00:33:30
reverse the camp license sex in a good
00:33:34
by injecting my finding it very
00:33:37
interested then now I'm thinking about
00:33:39
this in the context of brain protection
00:33:41
German fickle development particularly
00:33:44
with respect to cope with exposure. So
00:33:47
I want and by talking a little about
00:33:51
trans generational facts all people who
00:33:54
and this is an area that we've really
00:33:57
got into in the last two or three yes
00:34:00
the experiments again on that I can in
00:34:07
the guinea pig where we gave up you
00:34:09
record goes to the F zero mothers if
00:34:12
you like with and let the F one and and
00:34:16
those people we took the females loaded
00:34:18
the come from control numbers who could
00:34:20
come from people could could expose
00:34:22
mothers and we my to them with control
00:34:25
Miles they went through normally
00:34:27
pregnancy with none of further
00:34:29
treatment we then looked in all spring
00:34:32
up multiple time points in this work
00:34:34
was published a relatively recently in
00:34:36
and the chronology when we do that we
00:34:39
show that that was clearly and and the
00:34:41
current phenotype and about how
00:34:42
everything that I that these animals so
00:34:45
the animals too the young animals
00:34:49
they're exposed to sort of stress which
00:34:51
you know is right parts and activate
00:34:52
and the church original system when
00:34:54
he's looking normal animal so I'm not a
00:34:57
second generation females and I also we
00:35:00
see this robust response to the strains
00:35:02
press in those animals used grandmother
00:35:04
receive you coat cord that was a
00:35:06
planted wrists planted to trade real
00:35:09
response to and this one is stress that
00:35:14
these animals. Well hyperactive. We saw
00:35:18
that in the first generation female
00:35:20
second generation more all hyperactive
00:35:22
but these Miles actually have produced
00:35:25
activity in the open field so again
00:35:28
trans generational fax three maternal
00:35:30
transmission that highly sex specific
00:35:32
we've also recently got very
00:35:37
interesting the concept of paternal
00:35:38
transmissions okay we take the mild
00:35:41
offspring from these that's there are
00:35:42
mothers who received few athletes is
00:35:45
were exposed to record good we might
00:35:47
these animals with control females
00:35:49
these females go through normal
00:35:51
pregnancy we look up yeah to will and
00:35:53
to the sign to create the F three we've
00:35:57
got some very very interesting a
00:36:00
favourable and and the crane and a
00:36:02
transcript I mean information coming
00:36:06
from these which is gonna be presented
00:36:08
a the international diehard meeting
00:36:11
take down a kleenex model and hopefully
00:36:14
I can show you that later in the not
00:36:17
too distant future but with this idea
00:36:19
that paternal transmission is occurring
00:36:22
we got very interested in the idea of
00:36:24
how in fact this message might get
00:36:27
transmitted across generations how is
00:36:30
it possible that record corporate
00:36:32
explosion file that well that that
00:36:35
their offspring and subsequent
00:36:37
offspring and these studies to very
00:36:40
recent studies this study kinda my with
00:36:43
more she's if what we I did a very
00:36:45
simple experiment here in actually in
00:36:47
mice where we expose out a my all mice
00:36:50
to a syntactically report quote we then
00:36:53
what whitey to sperm cycles I'm not a
00:36:56
mess Elisha within this span we store I
00:36:59
decrease in on CEG relations associated
00:37:02
with record quite explosion in a apple
00:37:06
mice Tracy pile a calling from you can
00:37:11
has done some beautiful work in this
00:37:13
error this hyper that was published in
00:37:16
two thousand forty and what trying to
00:37:19
change is that I fathers a stress
00:37:22
either during the pretty Cuba period
00:37:24
will be out of period and she looks at
00:37:27
the of these animals there are increase
00:37:31
is in specific micro are nice. And in a
00:37:35
paper that I just us or actually last
00:37:38
night. And what's try seized on has
00:37:42
actually taken a selection of these
00:37:44
micro are amazed injecting them into a
00:37:48
fertilised embryos and shyness you can
00:37:51
read picture like the children doing
00:37:53
thing the types associated with
00:37:56
paternal stress so it doesn't look like
00:37:58
this micro nice carrying and important
00:38:00
signal okay so just someone then I'd
00:38:03
say that the prenatal environment I'm
00:38:06
not too specific about record could the
00:38:09
developing brain that I result in long
00:38:12
term changes in stress and
00:38:13
acknowledging behaviour I haven't shiny
00:38:16
the died today but we know that these
00:38:17
affects are dependent on the time of
00:38:19
exposure and this is actually really
00:38:21
important area that needs more work we
00:38:23
need to understand when there are
00:38:25
specific to sensitivity effects of
00:38:28
highly sex specific that I depend on
00:38:31
you have to look at multiple time
00:38:32
points around animals life pools to
00:38:35
understand how the what the impacts all
00:38:38
the effects of trans generational and I
00:38:40
think we'll start yeah now a pretty
00:38:42
good handle on the mac reasons by which
00:38:44
this project I mean is occurring within
00:38:47
the development right but with this new
00:38:50
knowledge we can study to harness it
00:38:53
and utilise it to identify by also is
00:38:56
it possible to take look for not by
00:39:00
Marcus perhaps a genetic by Marcus in
00:39:03
newborns to identify buttons you might
00:39:05
be Tristan this of developing finger
00:39:09
types associates group or I'm
00:39:11
associated with at first in pregnancy
00:39:13
and with that does this new knowledge
00:39:17
allow us to develop new novel Intel Jim
00:39:20
interventions to prevent or this the
00:39:24
effects with that I will finish and I
00:39:27
will acknowledge the five have done all
00:39:29
the work that I presented to die size
00:39:31
highly highly in right to to the
00:39:33
studies that showed you today think or

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Conference Program

Introduction to the 12th Nestlé International Nutrition Symposium
Thomas Beck, NRC Director
22 Oct. 2015 · 8:57 a.m.
416 views
Introduction to Session I - Cognitive & Brain Development
Susan Gasser, Friedrich Miescher Institute, Basel, Switzerland
22 Oct. 2015 · 9:04 a.m.
The development of a healthy brain
Michael Gazzaniga, University of California, Santa Barbara, USA
22 Oct. 2015 · 9:16 a.m.
219 views
Q&A - The development of a healthy brain
Michael Gazzaniga, University of California, Santa Barbara, USA
22 Oct. 2015 · 9:56 a.m.
Early influences on brain development and epigenetics
Stephen G. Matthews, University of Toronto, Canada
22 Oct. 2015 · 10:49 a.m.
Q&A - Early influences on brain development and epigenetics
Stephen G. Matthews, University of Toronto, Canada
22 Oct. 2015 · 11:29 a.m.
Building the physiology of thought
Rebecca Saxe, Massachusetts Institute of Technology, Cambridge, USA
22 Oct. 2015 · 11:38 a.m.
151 views
Q&A - Building the physiology of thought
Rebecca Saxe, Massachusetts Institute of Technology, Cambridge, USA
22 Oct. 2015 · 12:10 p.m.
Introduction to Session II - Cognitive Decline
Kathinka Evers
22 Oct. 2015 · 2:02 p.m.
Brain health & brain diseases - future perspectives
Richard Frackowiak, CHUV University Hospital, Lausanne, Switzerland
22 Oct. 2015 · 2:11 p.m.
Alzheimer's disease: genome-wide clues for novel therapies
Rudolph E. Tanzi, Massachusetts General Hospital, Charlestown, USA
22 Oct. 2015 · 3:15 p.m.
Q&A - Alzheimer's disease: genome-wide clues for novel therapies
Rudolph E. Tanzi, Massachusetts General Hospital, Charlestown, USA
22 Oct. 2015 · 3:59 p.m.
Immunometabolic regulators of age-related inflammation
Vishwa D. Dixit, Yale School of Medicine, New Haven, USA
22 Oct. 2015 · 4:21 p.m.
Q&A - Immunometabolic regulators of age-related inflammation
Vishwa D. Dixit, Yale School of Medicine, New Haven, USA
22 Oct. 2015 · 4:59 p.m.
Introduction to Session III - Nutrition & Cognitive Development
Pierre Magistretti, KAUST, Thuwal, Saudi Arabia and EPFL, Lausanne, Switzerland
23 Oct. 2015 · 9 a.m.
Energy metabolism in long-term memory formation and enhancement
Cristina M. Alberini, The Center for Neural Science, New York University, USA
23 Oct. 2015 · 9:16 a.m.
126 views
Q&A - Energy metabolism in long-term memory formation and enhancement
Cristina M. Alberini, The Center for Neural Science, New York University, USA
23 Oct. 2015 · 9:53 a.m.
Building the costly human brain: implications for the evolution of slow childhood growth and the origins of diabetes
Christopher Kuzawa, Northwestern University, Evanston, USA
23 Oct. 2015 · 10:29 a.m.
Q&A - Building the costly human brain: implications for the evolution of slow childhood growth and the origins of diabetes
Christopher Kuzawa, Northwestern University, Evanston, USA
23 Oct. 2015 · 10:57 a.m.
Nutrition, growth and the developing brain
Prof. Maureen Black, University of Maryland, School of Medicine, Baltimore, USA
23 Oct. 2015 · 11:09 a.m.
Q&A - Nutrition, growth and the developing brain
Prof. Maureen Black, University of Maryland, School of Medicine, Baltimore, USA
23 Oct. 2015 · 11:49 a.m.
Introduction to Session IV - Decline & Nutritional Intervention
Tamas Bartfai, The Scripps Research Institute, La Jolla, USA
23 Oct. 2015 · 12:48 p.m.
On multi-domain approaches for prevention trials
Miia Kivipelto, Karolinska Institutet, Stockholm, Sweden
23 Oct. 2015 · 1:04 p.m.
Q&A - On multi-domain approaches for prevention trials
Miia Kivipelto, MD, PhD, Karolinska Institutet
23 Oct. 2015 · 1:39 p.m.
Methodological challenges in Alzheimer clinical development
Lon S. Schneider, Keck School of Medicine of USC, Los Angeles, USA
23 Oct. 2015 · 1:49 p.m.
Q&A - Methodological challenges in Alzheimer clinical development
Lon S. Schneider, Keck School of Medicine of USC, Los Angeles, USA
23 Oct. 2015 · 2:32 p.m.
We are what we remember: memory and age related memory disorders
Eric R. Kandel, Columbia University, New York, USA
23 Oct. 2015 · 3:03 p.m.
136 views
Concluding Remarks
Stefan Catsicas, Chief Technology Officer, Nestlé SA
23 Oct. 2015 · 3:50 p.m.

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