Part 3 of 3: Stress and the Aging Brain

                 Perhaps where we see the most extensive effects of stress on the brain is in adulthood and into older age.  In rats, it has been discovered that acute and chronic stress can have very different effects.  An acute stressor (ie. something that only lasts for a short period of time) actually enhances learning and memory, up to a certain point, beyond which too much stress causes performance to deteriorate again.  A state of chronic stress, however, has been shown to have very negative effects on the brain.  Specifically, in rats, chronic stress has been associated with a shrunken hippocampus, specifically because dendrites in the hippocampal neurons begin to die off.  These rats also perform more poorly on memory tasks, especially those involving spatial memory. 

                In fact, if you expose a middle-aged rat to high levels of glucocorticoids, it will perform cognitive tasks similar to the way that a rat in old age would perform them, while reducing glucocorticoid levels in an old rat will enhance its performance.  So, could chronically high glucocorticoid levels contribute to the cognitive decline (memory and word-finding difficulties) that we know happen as we age?  Could they have anything to do with Alzheimer's Disease (AD), a disease characterised by both poor memory and reduced hippocampal volume?  The answer so far is that we're still not sure, but more and more evidence is suggesting that there is at least a correlation between chronic stress, a smaller hippocampus and the prevalence of Alzheimer's.  In monkeys, higher glucocorticoid levels have also been shown to increase Beta-amyloid in the brain, a protein that's known to be a precursor to the cell death seen in Alzheimer's Disease. 

                But why is this?  If you remember back to my first post about stress and the brain, I said that the hippocampus is one of the main mechanisms by which the HPA axis gets shut down.  If you have more and more glucocorticoids, you see hippocampus shrinkage.  This means that there's less and less hippocampal tissue to shut down the HPA axis, leading to chronically high glucocorticoid levels and consequently, a chronically shrinking hippocampus.  It's a feed-forward mechanism.  There's also the neurotoxicity hypothesis, which says that a lifetime of dealing with chronically high glucocorticoid levels may cause the hippocampus to be less able to deal with other aspects of normal aging and therefore its cells are more easily damaged and die off. 

                Don't panic yet.  There's no need to stress out about how your brain is responding to your stressful life.  You're not doomed to an ever-dwindling hippocampus.  It turns out that if you remove a chronic stressor, dendrites that had previously disappeared are actually able to grow back.  Obviously removing every stressor from our lives isn't likely to happen, so there are a few other minor changes that we can make to help us along.  Interestingly, one of the few things that we can do in order to grow new neurons (called neurogenesis, a phenomenon that neuroscientists only came to believe in fairly recently) is exercise.  Exercise has been shown to especially increase neurons in…wait for it…the hippocampus.  How convenient is that?  As if we needed another incentive to stick to our 2011 resolution to hit the gym! 

Cristina McHenry

Concordia University

Adapted from "Effects of Stress Throughout the Lifespan on the Brain, Behaviour and Cognition" by Sonia Lupien et al. and inspired by Wayne Brake's Neuropharmacology course at Concordia University.