Short-term sleep disturbance enhances brain-derived neurotrophic factor gene expression in rat hippocampus by acting as internal stressor.

Abstract

Rats were subjected to nonselective sleep disturbance for short periods under conditions designed to minimize the adverse influence of external stresses, such as environmental conditions and restricted movement, and both brain-derived neurotrophic factor (BDNF) protein and its mRNA levels in the brain were then determined to investigate the influence of sleep disturbance itself on BDNF gene expression. Total sleep duration was partially but significantly reduced by disturbing the sleep/wake cycle for 1 and 2 h, gradually increased according to the time of disturbance, then returned to control levels at 6 h after the beginning of sleep disturbance. Under these conditions, the slight but significant elevation of corticotrophin-releasing factor (CRF) mRNA levels in the paraventricular nucleus (PVN) was observed at an early stage of the sleep disturbance period. Sleep disturbance induced the elevation of both BDNF protein and its mRNA levels in the hippocampus but not in the cerebellum or the brainstem, and the elevated BDNF mRNA expression in the hippocampus returned toward basal levels during the sleep recovery period when the rebound of sleep duration was observed. These findings suggest the possibility that short-term disturbance of the sleep/wake cycle and, hence, the partial reduction of non-REM sleep duration, might exert a potential influence on neuronal and/or glial cells as an internal stressor, resulting in the elevation of BDNF gene expression in rat hippocampus.