Aging Brains, Stress and Alzheimer’s: A Correlation? | Kellie Tamashiro, Ph.D.


>>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.

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