Stress-Induced Neurodegeneration: The Potential for Coping as Neuroprotective Therapy

Abstract

Stress responses are essential for survival, but become detrimental to health and cognition with chronic activation. Chronic hypothalamic-pituitary-adrenal axis release of glucocorticoids induces hypothalamic-pituitary-adrenal axis dysfunction and neuronal loss, decreases learning and memory, and modifies glucocorticoid receptor/mineralocorticoid receptor expression. Elderly who report increased stress are nearly 3 times more likely to develop Alzheimer's disease, have decreased global cognition and faster cognitive decline than those reporting no stress. Patients with mild cognitive impairment are more sensitive to stress compared to healthy elderly and those with Alzheimer's disease. Stress may also transduce neurodegeneration via the gut microbiome. Coping styles determine hippocampal mineralocorticoid receptor expression in mice, indicating that coping modifies cortisol's effect on the brain. Identifying neuroprotective coping strategies that lessen the burden of stress may prevent or slow cognitive decline. Treatments and education designed to reduce stress should be recognized as neuroprotective.

Keywords: Alzheimer’s disease (AD); cognition; coping; hypothalamic-pituitary-adrenal (HPA) axis; neurodegeneration; stress.

Figure 1.

The response to stress in relation to allostasis or allostatic overload. The brain, our main controller of stress, regulates the autonomic nervous system, sympathetic nervous system, and neuroendocrine system. The status of these systems in conjunction with individual behaviors and differences determines the effect that stress has on health. (Adapted from.).

Figure 2.

Stress-induced glucocorticoid levels correlate with changing MR and GR occupancy ratios. Diagonal lines and horizontal lines indicate relative bound MR or GR, respectively. * indicates when consolidation is improved. # indicates when retrieval is impaired. (Adapted from.).