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.