Behavioral and Biochemical Consequences of Early Life Sleep Deprivation in Rats

Adequate sleep is essential for normal brain function, especially during the critical period of early developmental stages (childhood and adolescence). Many epidemiological and clinical studies have linked early life sleep deprivation (SD) with the occurrence of later life behavioral impairment. However, the mechanism by which early life SD causes behavioral impairment is not fully understood. Animal studies have provided useful insights. Previous reports from our laboratory have suggested a potential role for oxidative stress in induction of behavioral impairments in a rat model of acute sleep deprivation. Others have reported that extended wakefulness increases cellular metabolism and induces formation of reactive oxygen species leading to oxidative stress. Moreover, synaptic pruning and neuronal myelination occurs during early life. These processes are essential for neural circuitry maturation which underlies the behavioral changes. Sleep enhances synaptic pruning and neuronal myelination, strengthening neuronal connections. Therefore, we suggested that sleep deprivation during early life, by engaging stress pathway(s), adversely affects neuronal development and function leading to long-lasting behavioral impairment. We examined the effect of early life SD in rats. The rats at postnatal day (PND) 19 were exposed to SD 6-8h/day for 14 days. The behavioral consequences of SD were examined at different developmental stages; early adolescent: PND33, late adolescent: PND60, and adulthood: PND90. The biochemical markers of stress and synaptic density/ plasticity were measured in different brain regions at PND33 and PND90. We found that anxiety-like behavior was induced in SD rats at early life (PND33 and 60). However, at later life (PND90), anxiety-like behavior disappeared and depression-like behavior developed. Interestingly, we found a reduction in synaptic density and plasticity in prefrontal cortex (PFC) of SD rats at PND33 and PND90 as compared to control rats. The protein level of the stress response phosphatase (MKP1), was upregulated while the protein level of the neurotrophic factor (BDNF) was down-regulated in PFC of SD rats. The results suggest that PND 19-32 in rats (2-11 years in humans), is a sensitive period to SD. Sleep deprivation during this developmental stage alters cortical maturation most likely by reducing synaptic density and plasticity contributing to the behavioral deficits.