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).
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!
Edit: Travels with Darwin posted a summary of the last part of Sapolsky’s talk focusing on his primate work.