Memory dysfunction at high altitude: Role of corticosterone

Exposure to stress is always accompanied with elevated corticosterone synthesis and secretion. Elevation of corticosterone is essential for initiation of adaptive physiological alteration in the body system. However, prolonged elevated corticosterone in plasma as well as tissue incurs disruptive damage causing mal-adaptation to stressors. This biphasic response of corticosterone depends on types, intensity and duration of stress exposure. Hypobaric hypoxia, a low pressure oxygen condition unique to high altitude region is such a stressor. Mal-adaptation to high altitude causes acute mountain sickness, high altitude pulmonary and cerebral edema and decline in cognitive functions. Maintenance of optimal corticosterone concentration in plasma and hippocampal region of brain and inhibition of glucocorticoid receptor ameliorates hypobaric hypoxia induced memory dysfunction. Withanolide enriched extract of Withania somnifera root reverses hypoxic damage to hippocampal neuron by modulating corticosterone signaling through nitric oxide-cyclooxygenase-prostgalandin pathway. Modulating corticosterone level provides better therapeutic strategies for stress related disorders.