Stress and Its Influence on the Brain

Biological stress is produced within the brain by actual and perceived threats. The physiological effects caused by stress serve as a protection mechanism for both the body and the brain, at least during the initial dangers. However, prolonged exposure to stress culminates in severe negative consequences. Neuroscientific research has only recently started to explore the complex relationship between stress, brain activity, and possible brain damage.

The release of cortisol, a steroid hormone produced by the adrenal cortex, is a direct consequence of stress. This hormone circulates through the bloodstream to the brain, where it binds to receptors located in the cytoplasm of numerous neurons. Once activated, these receptors migrate to the cell nucleus and promote gene transcription, leading to protein synthesis. One of the most important effects of cortisol action is the increased entry of calcium ions (Ca²⁺) through voltage-gated ion channels in neurons. This effect may stem from changes in channel function or in the cell's energy metabolism. On a short-term basis, cortisol seems to strengthen the brain's capacity for dealing with stress—the brain possibly developing strategies to mitigate its consequences.

| Chronic stress is a different matter. As too much calcium is highly toxic—it will kill neurons (excitotoxicity). So the question is, can cortisol be fatal? Scientists like Bruce McEwen of Rockefeller University and Robert Sapolsky from Stanford University have used rat models to test this hypothesis. Their results suggested that chronic daily treatment with corticosterone, the rat counterpart of cortisol, for a few weeks led to marked dendritic regression of neurons that expressed corticosterone receptors. Several weeks later, these neurons were seen to degenerate. Similar effects were observed in stressed rats that received no hormone injections.

For instance, studies by Sapolsky in the natural habitat of wild baboons in Kenya illustrate the consequences of chronic stress. Here, the baboons establish complex social hierarchies and, often, subordinate males learn to avoid dominant males as much as possible to avoid stressful situations.

| In a year in which the baboon population had exploded, nearby villagers started capturing many of these baboons to protect their crops. Unfortunately, captive dominant baboons suffered massive mortality of subordinate males, without apparent injuries or starvation, but apparently due to exacerbated and chronic stress. Those baboons were suffering from severe health problems, including gastric ulcers, colitis, enlarged adrenal glands, and very significant neurodegeneration in the hippocampus. Subsequent research explains that the hippocampal damage is from the direct effects of cortisol, a hormone related to stress. The outcomes of stress and exposure to cortisol on the brain are largely similar to those presented by aging. The given studies have clearly shown that chronic stress dramatically accelerates aging in the brain.

Trauma that is experienced by a human subject can range from warfare, sexual violation, and cruel acts of violence; post-traumatic stress disorder (PTSD) is eventually developed by such exposure. Individuals suffering from PTSD characteristically exhibit heightened anxiety, memory impairment, and intruding thoughts. Neuroimaging research has consistently shown degenerative changes in the brains of affected individuals, particularly in the hippocampus.

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