Stress and your brain

sapolsky

I just returned from a lecture by Dr. Sapolsky on the campus of UC Davis. This guy does some awesome research!  And has some awesome hair!  Here is a synopsis of his talk:

When an individual (human or otherwise) encounters a particularly stressful situation, their body releases glucocorticoid hormones in response (e.g., cortisol release in people). These hormones divert energy away from numerous bodily functions and send that energy to important muscles that your body may need to help you escape. For example, your body will put off ovulating for awhile so that the energy can instead go to your thighs, which need to quickly carry you away from the predator at your heels.

When stressors are acute and stress responses infrequent, then this system works wonderfully. Unfortunately, organisms in highly social societies (e.g., primates like ourselves) often experience frequent, chronic stress. This means that our stress hormone levels are frequently high and are continuing to divert energy away from particular bodily functions in order to prepare it for use elsewhere. One area where this is especially a problem is in the part of the brain known as the hippocampus (important in long term memory and spatial navigation).

neurons_ucd

The hippocampus has lots and lots of glucocorticoid receptors. When an individual is frequently stressed, then energy is frequently being diverted AWAY from hungry neurons in this region. Neurons in chronically stress individuals are therefore experience a state of near constant low energy. Most of the time, this low energy state does not result in neuron death.

Unfortunately, extremely high stress situations (such as strokes, gran mal seizures, etc.) can push the neurons past their tipping point, resulting in cell death and a loss of brain mass in the hippocampus. After an event such as a stroke, the body maladaptively (but understandably!), responds by releasing more stress hormones. This causes further energy deprivation to the neurons, knocking many of them out.

So what can we do to preserve neurons after events such as strokes? You can inhibit the body from producing glucocorticoids, you can bind up glucocorticoid receptors in the hippocampus so they can’t respond to the glucocorticoids, or you can supply the hippocampus with additional nutrients to make up for the energy loss. The problem with these three solutions is that they’re mainly effective if you implement them very soon after the event and they can only dampen negative effects.

The Sapolsky lab has recently been working on an awesome new solution to this problem. While cortisol is associated with neuron death, estrogen seems to have a regenerative effect. So how do you get the hippocampus to release estrogen in response to increasing cortisol levels? The answer: surprisingly, gene therapy through the use of VIRUSES.

Viruses inject themselves into cells and direct the cells to produce particular proteins that the virus requires in order to replicate. Scientists now use viruses to direct cells to create proteins that code for particular proteins that scientists would like the cell to produce.

Here is the genius of the Sapolsky Lab. The lab has manufactured a virus that gets cells to produce a protein that is BOTH a glucocorticoid receptor and a molecule that binds to estrogen receptors. In anthropomorphic terms, this protein knows when stress levels are up and goes to estrogen receptors to tell cells to start producing estrogen. The result is neuron regeneration INSTEAD of neuron death after super stressful events.

Although this solution is brilliant, it comes with some serious drawbacks. First, it requires purposefully introducing a virus into a patient. Even worse, lots of the viruses that are the most suited for this technique are related to pretty nasty viruses. There are fears that a virus may sometimes recover its ability to become infective once it is in the patient and the possibility also exists that the patient’s body will recognize the disease as foreign and mount an immune attack against it. Unfortunately, the problems don’t end there.

The viral vector also needs to be introduced directly into the hippocampus. It would be a bad thing for the entire human body to begin upregulating estrogen in response to stress, so it’s important that the virus injection be targeted. One of the only methods for getting the viral vector into the hippocampus is to use a needle to inject it directly. Clearly, you will not be able to drill a hole and inject a needle into the head of a patient experiencing a gran mal seizure. You don’t really want to be removing the skull cap of stroke victims either. At the moment, there is no clear solution. Dr. Sapolsky even postulates that, if this problem isn’t solved in the next decade or so, then you can expect funding for this area of research to dry up real fast.

Kind of makes you wish research on nanobots (robots that work at super microscopic scales) were moving along faster, huh? If we could manufacture nanorobots to deposit these viral vectors in the hippocampus, the problem would be solved. Unfortunately, these tiny biological works are more theoretical than anything at the moment.

While no biological nanobots have been created at this time, work on nanomachines has been progressing. The Tour Lab at Rice University was able to create a “nanocar”, the movement of which could be controlled through the use of a scanning tunneling microscope.  It seems promising to me that we’ve at least figured out how to manufacture molecular robots and have figured out how to direct their movements!

Hopefully science comes up with a way to safely utilize the Sapolsky Lab’s viral invention. In the meantime, you should check out some of Sapolsky’s books!

whyzebrasdontgetulcers

Monkeyluv: and Other Essays on Our Lives as Animals

Junk Food Monkeys

Why Zebras Don’t Get Ulcers 

 

EditTravels with Darwin posted a summary of the last part of Sapolsky’s talk focusing on his primate work

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30 thoughts on “Stress and your brain

  1. Hello, We, the masses, have been sent by someone you know and are going to marry to tell you how well you are doing. Unfortunately, I have no idea about all this science stuff except for what nanobots do in movies and who robots will one day take over the world and us along with them.

  2. how cool is that? i have a friend studying nano at uni in Australia, at least you know nano is increasing in uses all the time and its advancing at a nice pace too 🙂

    • Hey, Mitch. Do you happen to know about any neat advances on the nanobot front? Are we still in the completely theoretical stages or is there some progress?

      Thanks for commenting!

  3. Also sent by the comic guy.
    But it doesn’t look like the nanobots angle won’t pan out for some time.
    In the meantime, what can we do to protect our neurons?

    • Your neurons will likely be fine as long as you don’t suffer a stroke, seizure, etc.

      That being said, the best thing you can do is to probably figure out which behaviors and activities help you destress and be sure to do those regularly!

  4. Also sent by said Comic Book Guy. But I love this science jazz, so thanks for writing this stuff. I wish we got characters with crazy hair at the lecture things I go to, instead of the suit’s…with nice suits we get.

  5. Hi Kelly, great blog, I was sent by the comic guy but I’ll be grabbing your RSS feed when I get home.

    LeeJH, it’s important to note that this treatment would only be applicable after high-stress events like strokes, and like any treatment would probably only be used in conjunction with lifestyle changes (in this case to reduce chronic stress.) There are other stress-related ailments that a hippcampal (sp?) injection probably wouldn’t help (heart weakness, ulcers, etc.)

    Also, screw nano-bots. I’m investing in power-drill based delivery systems. How much is Home Depot stock trading at these days?

    • For example, a commonly used lentivirus is created from the human immunodefiency virus (HIV-1). This virus allows them to inject lots of genetic material into the host cell, which allows scientists to tell cells to create proteins that require long codes to create. Additionally, this viral vector will persist in the patient longer than some other commonly used viral vectors.

      Honestly, this technique is pretty far outside my realm of “expert” knowledge. All I know about this technique is what I learned in a behavioral genetics class with Dr. Brian Trainor awhile back, but I hope that helped!

  6. Ditto to #10.
    I really appreciated that you wrote this in an easily read format for non-science people! It’s a gift, it really is. Most of us can’t translate the two back and forth very well like that, so kudos!
    Has Sapolsky developed the virus so that it is restricted to the hippocampus once injected? Because you’re right: an analog of estrogen would have dire effects if let loose throughout the body.
    [Minor nitpicky grammar thing: “responses” is not a verb. Just fyi.]

    • I believe Sapolsky’s virus will stay restricted to the hippocampus once injected. I believe that the deal with using this type of procedure is that the virus only infects cells adjacent to the injection point. Because the virus has been genetically engineered, it doesn’t replicate itself and therefore doesn’t move far past the point of injection.

      Thanks for reading! Also, thanks for the grammar tip!

  7. Hi, I’m an advanced (?) medical student and teaching aid in physiology, with special interest on neurophysiology and stress response. Sapolsky has always been an important reference in the field.

    However, one must always tread carefully when describing potential benefits of, as of yet, unproven medical interventions. What may seem perfectly logical in theory does not always translate to patient benefit (I particularly remember a clinical trial of beta-blockers for heart failure, which had to be stopped prematurely due to unforseen increases in mortality in the beta-blocker group!).

    Anyway, I love your blog and intend tore ad more of it. Could I please ask you to post links the original source material (PubMed or other such databases links)? So we can comment in a more informed way 😀

  8. This was a really well written post; thanks for writing it. You seem knowledgeable on the subject which, even when talking about somebody else’s talk, increases the quality drastically. I really look forward to reading more of your blog.

    By the way, “A Primate’s Memoir” by Sapolsky is a great book. Shortish read, but a lot of education and entertainment rolled up in to a 25 year story of his field work with baboons.

    I am biased, however, since primatology is one of my favorite topics.

  9. Yet another drone sent by the comic guy.

    This blog looks like it’s right up my alley, though (almost done with B.A.s in Molecular & Cellular Biology and Psychology). This post in particular amuses me because the advisor in the lab I work in loves this guy and all the things he talks about.

    Last I heard, supplemental estrogen had mixed effects on the brain. If given to post-menopausal women too long after menopause (~10 years, I think), it can actually accelerate neurodegeneration associated with age and particularly Alzheimer’s. That’s not to bash its pro-growth properties, which it indeed does seem to have under certain circumstances. I suppose I’ll look into this more…

    Very interesting!

  10. Very good read. It was very informative and easy to read. Good work.

    There are a few typos that you might want to be aware of(they didn’t bother me, but I figured since you were writing in a professional matter you would care). In the 4th paragraph from the bottom need should be needle and solve should be solved. That is all 🙂

  11. I’ve never been a big fan of viruses for gene therapy (Wasn’t that the plot for I Am Legend?). I recently read a paper where a group was able to use iPS cells to add a corrected version of a hemophilia-inducing gene to the bone marrow of mice and cured their hemophilia. I feel like you could do something similar for the hippocampus, though obviously the brain is a much more complicated beast. Did anything like that come up?

    • Unfortunately, nothing like that did come up. It sounds pretty cool though and I definitely plan on reading up on that soon!

      Thanks for the comment!

  12. Grae, you beat me to it–Primate’s Memoir is a great book. It’s actually a great representation of what working as a primtatologist can actually be like.

    One of my favorite bits of the talk (I’m biased, since I study primate foraging behavior and thus mostly have a casual interest in stress) was Sapolsky’s description of how one goes about darting a baboon. Apparently getting glucocorticoid baselines is tough when you have to make sure you get a baboon before they’ve eaten, when they aren’t nutritionally or socially stressed, when there are no predators around, without them seeing you, with a tranquilizer that doesn’t interfere with these levels.

    A lot of A Primate’s Memoir is in the same vein, which means its basically candy to anyone like me who can’t wait to get back to the field.

    Hi Kelly! I (sadly enough, since I actually know you) found your blog through the comic as well–keep up the interesting stuff!

    • Some of the stories about dartings gone wrong… The book is worth purchasing (or borrowing from a library) just for those!

  13. Yay for sciency grad student blogs!
    Welcome to the community!

    I’m also not sure we’re close to virus-delivered gene therapy, so it’ll be interesting to see how this field unfolds.

  14. I’m much more inclined towards physical sciences like physics and chemistry than I am towards biology and the like, but this is a pretty interesting blog entry. Also came here through Zach’s comic. Enjoyed reading the blog entry, pretty fascinating even despite it not being my area of interest. Look forward to reading future blog entries.

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