0046 IMPACT OF EARLY LIFE SLEEP DISTURBANCE ON BEHAVIORAL PARAMETERS IN RATS: POTENTIAL ROLE OF OXIDATIVE STRESS MECHANISMS

Abstract

Adequate sleep is essential for normal brain function. Many epidemiological and clinical studies have linked early life sleep disturbance (SD) with behavioral and cognitive impairments. However, the mechanisms by which early life SD causes behavioral and cognitive impairments are not fully understood. Extended wakefulness increases cellular metabolism and induces reactive oxygen species formation leading to oxidative stress. And, the brain is considered highly susceptible to oxidative stress because of its high oxygen consumption. Therefore, we suggest that SD at early life stages, by engaging oxidative stress cascades, might adversely affect neuronal development and function leading to behavioral impairment. We examined the role of oxidative stress on behavioral impairment caused by early life SD in rats, at postnatal day (PND) 18. Two groups of Sprague Dawley rats (12 per group) were employed, control and sleep disturbed (SD) groups. Rats at PND18 were subjected to SD for 14 days (6-8h/day) using Pinnacle sleep deprivation system. Behavioral tests (anxiety and depression-like behaviors) were performed at PND32, 60 and 90. Blood samples were collected at PND32. SD rats exhibited anxiety-like behavior at PND32 and 60 but not at PND90 as compared to the control rats. Interestingly, SD rats did not exhibit depression-like behavior at PND32 or 60 but developed depression-like behavior later at PND90, as indicated by increased immobility time in forced swim test compared to control rats. Plasma levels of corticosterone (indicator of stress) and 8-isoprostane (marker of oxidative stress) were significantly increased in SD rats compared to control rats. Early life SD promotes anxiety-like behavior early in life (PND32 and 60) which in later life transforms into depression-like behavior (PND90). The increase in oxidative stress markers in the blood following SD protocol, is suggestive of a potential role of oxidative stress in later life behavioral impairment. 2R15MH093918-02.