P2‐023: SLEEP DEPRIVATION INDUCES COGNITIVE DYSFUNCTION THROUGH MECHANISM INVOLVED IN NEUROINFLAMMATION AND OXIDATIVE STRESS

Prolonged sleep deprivation (SD) is stressful and the consequences of SD bring detrimental influences on health and cognitive function. Melatonin (MEL) is an effective chronobiotic agent. Several lines of evidence demonstrated that SD has potent neuroprotective properties in a number of animal experimental models. In this investigation, we tried to address how SD induces cognitive dysfunction and to see if administration of MEL could restore the cognitive dysfunction induced by SD. We employed SD model in Wistar rat. The experimental animals were divided into 5 groups as the followings: (1) normal control (NC, n=6); (2) MEL group (n=6); (3) SD group (n=8); (4) stress control group (n=7); (5) SD with MEL (n=8), MEL (10mg/kg/day) was introduced intraperitoneally for 1 week before and during SD procedure. The Morris water maze task (MWM) was used for testing hippocampal dependent memory. Subsequently, histological investigation was performed to assess neuronal cell death, neuroinflammation and oxidative stress. Group on SD for 72 hr showed poor performance in MWM compared to NC (P<0.05). Glial activation in the hippocampal field was pronounced in SD compared to NC, however there was no difference in neuronal death between groups. 4-HNE immunoreactivity was increased in SD which was attenuated by MEL treatment. The underlying mechanism of this observation was thought to be associated with fragile X mental retardation gene 1 protein (FMRP) upregulation. These results suggest that SD cause cognitive dysfunction through neuroinflammation together with oxidative stress. Treatment with MEL suppresses SD-induced neuroinflammation and oxidative stress via mechanism associated with FMRP upregulation, hence reverse SD-induced cognitive decline. MEL and related compound might be useful in managing cognitive dysfunction seen in neurological disorder such as autism and Alzheimer's disease.