>> Thank you very much.
It's a pleasure to be here today
to share some of the work that we're doing in the lab.
Focusing on aging and the aging brain
and how that's more susceptible to stress.
So this a broad overview of what I want to talk about today.
I'm going to define stress, first of all,
and then talk about how that effects the aging brain
and can lead to cognitive deficits broadly.
And talk a little bit about what I think is
the hopeful aspect of our research.
And that is to determine if we can find an interventions
to prevent and treat these conditions.
So stress, everybody says they've experienced stress.
It can come from giving care to a loved one who's ill.
Actually, the caregivers stress is one of
the most significant stressors
and does increase the risk for Alzheimer's disease
according to some epidemiological studies.
Many of you are probably familiar with this
in not having enough hours in a day to meet your deadlines.
I certainly don't have enough.
For me and many of my colleagues here,
the stress of obtaining a chunk of that limited NIH budget
is always a consistent and chronic stressor for us.
Certainly, we're all familiar with
the current political climate.
And so all of these together can exert a strain on the body.
And we need to be able to cope with these stressors.
The word stress is actually derived
from the field of physics.
So Hans Selye first coined the term,
took the term stress and applied it
to this strain that we experience.
And that's why we use that term, stress.
And it usually has a negative connotation
but really I want to emphasize that
we need to have a stress response in order to survive.
And this is just a very brief cartoon of
a normal healthy stress response.
And as you can see here, a stressor like the lightening bolt
hitting your head here activates the
hypothalamic pituitary adrenal access.
This initiates a whole variety of physiological responses
that are normal and it should help us to cope
with a stressor once we encounter it.
One of the most important aspects of this system
is feedback, so this negative feedback arrow here
tells our brain to stop once the stressor is
no longer a threat to us.
And hopefully that's what will happen
when I step off this stage for me.
(laughs)
so this is a tightly regulated response,
it's a normal response that I mentioned earlier.
And it helps us cope with stressors.
However, if we're exposed to chronic stress
or if this system somehow becomes dysregulated
and chronically turned on, for example.
We're chronically turned off.
It can result in a variety of different conditions.
We're usually associating chronic stress
with development of depression, anxiety-like behavior,
anxiety and psychiatric conditions.
But it's also associated with developmental things
like cardiovascular disease and diabetes
and impairments in reproductive function.
So how does this stress and chronic stress
impact the aging brain?
The aged brain is more susceptible to stressors
and we are using animal models in the lab,
I'm a basic scientists.
And we use mouse models to study
how stress effects the brain.
And so in this experiment we took old and young animals
and we exposed them to a variety of different stressors
over the course of two weeks.
And then we asked them to tell us about
their learning and memory.
So we asked them to solve a maze.
And in this paradigm, animals that learned the maze
effectively, like these normal, non-stressed animals
shown here in blue, will solve it quicker and quicker
over the course of time.
We find that these young stressed animals
were slower to learn this task but eventually did learn it
and could remember it.
But as you can see here on the top,
the aged stressed animals just didn't learn it
and, of course, couldn't recall it in the end.
And working in the field by many, many others
have identified different regions of the brain
that we know are influenced by the stress
and are also involved in cognitive function.
And I'm gonna just show you a little bit of data, oops.
This is going the wrong way.
Okay.
A little bit of data from the hippocampus here.
And I really like this brain region,
not only because it's involved in my research
but it has a cool name.
Hippocampus actually means seahorse in Greek.
And it's because if you pull out that hippocampus
from your brain it looks like the shape of a seahorse.
And what you see here on the right side, sorry.
Is the image of the
human hippocampus.
So we look at the neurons in this region
following chronic stress, you can see there's
a significant amount of remodeling in the stressed animal
compared to the control animal.
They have much less branching.
And if we terminate the stressor and let them recover,
what you find here,
so this is the structure in young, middle age,
and aged animals that have experienced a stressor.
And you see significant remodeling in all these groups.
But if we let them recover, you see that
the young animals are able to compensate for that.
They recover that branching.
A little attenuated in the middle aged animals
but in the aged animals, there really isn't any
recovery evident at all.
And so there's a persistent change here in the hippocampus
and what we're interested in is, how does this happen?
But also, how can we intervene
and perhaps prevent this from happening?
So you remember these data.
I showed you that the aged stressed animals
don't learn very well.
So we took some old animals and we stressed them again,
but before we did that,
we gave them some environmental enrichment.
So typically, mice are housed in these standard cages.
It's relatively barren except for some bedding materials.
But we gave some of these mice enriched cages
where they had some toys to play with, it was a larger cage,
and they could afford a little bit more activity.
And so we took the animals,
we gave them these cages for a couple of weeks
and then stressed them for a couple of weeks.
And when we asked them to solve that maze task again,
what you can see here is that the aged stressed animals,
yes, they can't learn this task.
But those that had the enriched cages actually look more
like the control, non-stressed animals.
And so it suggested that we either prevent it
or able to mitigate some of that change in the brain.
We're currently pursuing different mechanisms
responsible for this.
Now, jumping into the human, does this also occur in humans?
This is one study that took older adult
who were 65 to 67 years old,
there are 120 people in this study.
And what they did is they took images of their brains
before and after an intervention over
the course of one year.
And so people either had exercise,
this was moderate, aerobic exercise over three days a week.
Versus people who were just given some stretching exercises.
And what they found is after a year,
the volume of the hippocampus, so in here,
was larger in the people that had the exercise intervention.
It was specific to this brain region.
So other brain regions didn't show any changes in volume.
And these people also performed better
when they were given a learning and memory task.
So suggest maybe some exercise
or some type of intervention enriched environments can
affect the brain and have beneficial consequences.
And certainly, based on some of the work that
Dr. Julanier has done and many others,
we do know now that the brain is dynamic,
it is plastic, the neurons can shrink and expand,
they can change, we can change the connections.
They disappear but they may be replaced
and we may be able to encourage that
by doing some of these types of interventions.
And certainly, some new neurons continue to grow
in some of the places in the brain.
And we may be able to take advantage of that.
So some of the just general take home messages,
I just wanna emphasize again that stress
is an inevitable part of our life, of course.
But the response to that stress is normal
and physiological and critical for our survival.
But when it's chronic or dysregulated
that it has a deleterious consequence on
brain function and behavior.
And it's becoming more and more clear
that the aged brain is more susceptible to chronic stress
and is also less able to adapt.
But at least some of our basic science studies
have demonstrated that we can intervene
and hopefully take advantage of trying to do this
with patient populations as well.
And finally, I think that identifying biomarkers,
or markers of brain function is something
that we're really very interested in.
Because it's hard to take a, you can't take a biopsy
of the brain to see what it's function is.
But if we identify different molecules in circulation,
perhaps, that could give us a window
into what the brain is doing
and give us an idea about it's health.
Finally, I just wanna acknowledge a lot of my colleagues
at Hopkins, as well as our collaborators
that have been involved with this work.
Thank you.
(audience applauds)
>> I have a question for you.
So in the human setting.
>> Yes.
>> You have an experimental model for stress.
In the human setting, you think about chronic stress.
What are your distinctions between chronic stress
and what you say, day to day stress?
>> So I would think, that example that I gave earlier on
with the caregiver stress,
that's a chronic, it's unpredictable,
and it's quite severe.
You care about this loved one
and they're suffering, you don't want them to suffer.
And actually, that's one of the most significant types
of stressor in addition to losing a loved one.
I think that caring for these people
that are in these situations
and I think that population's gonna grow
more and more very quickly.
That we can hopefully intervene
and prevent negative consequences from happening.
>> Thank you.
>> Thanks.
>> Thanks very much.
>> Man: If you go into many assisted living centers
and I guess, older communities.
What can you do in these situations?
I see people just sitting around doing nothing almost.
And I wonder,
your works in terms of enriching the environment.
Any studies going on there that may have
an impact in that area?
>> So thinking about the animal model
and translating it into the human situation
I think of it as encouraging social contact
and more activity, of course.
You mentioned that they're just kind of sitting around
and there's really nothing going on.
But I think engagement, social support,
and I think Dr. Lyketsos is gonna talk about
some of the interventions that they're doing
with Alzheimer's care givers.
And that could also have beneficial effects
in keeping the ones at home
and keeping them in a comfortable environment.
But also taking care of those caregivers
that are under significant stress too.
>> Thank you so much.