Chronic sleep fragmentation (SF) is characteristic of aging, sleep-related breathing disorders, and neurological and psychiatric diseases, including major depressive disorder (MDD), all prevalent in the veterans population. SF induces cognitive deficits in animals and humans, but the mechanisms underlying these deficits are unknown. We study adult hippocampal neurogenesis, a process which facilitates specific cognitive functions which are impaired by SF. Markers of oxidative stress are found in brains of MDD patients, and are predicted to affect cells with high metabolic activity, including parvalbumin (PV+ neurons) which regulate hippocampal adult neurite survival. We will examine effects of SF on oxidative stress in PV+ neurons and neurite survival, behavioral changes resulting from deficits in neurite survival, and responses to anti-oxidant treatments. Since infection and fever often precede MDD and other neurological conditions, and fever exacerbates oxidative stress, we will examine the interactions of elevated brain temperature and fever, SF, and oxidative stress. Results will provide a basis for protecting personnel from these forms of brain damage.
Proposed studies will elucidate the mechanisms underlying the effects of sleep fragmentation (SF) which is prevalent in human neuropsychiatric disease. Major depressive disorder (MDD) and post-traumatic stress disorder patients exhibit GABAergic abnormalities, including parvalbumin (P+) neuronal abnormalities; PV+ neurons are susceptible to oxidative stress. We will determine how SF and oxidative stress lead to PV+ neuronal and cognitive deficits. Proposed work could identify a basis for expanded use of anti-oxidant treatments of MDD and other neurological disorders, and the aggressive control of fever and other causes of elevated body temperature, including in military operations.
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