Early Life Sleep Deprivation: Role of Oxido-Inflammatory Processes

The adverse consequences of early-life sleep deprivation on mental health are well recognized, yet many aspects remain unknown, therefore, animal studies can offer useful insights. Male Sprague-Dawley rats at postnatal day (PND) 19 were subjected to sleep deprivation (SD) for 14 days (6-8 hours/day). Control (CON) rats were gently handled. Behavior tests were done on PND33, PND60 and PND90. SD rats exhibited anxiety-like behavior at PND33 and PND60, when compared to CON rats. Depression-like behavior was observed at PND90. Evaluation of oxidative stress and inflammatory markers revealed interesting results. Plasma 8-isoprostane and antioxidant defense enzymes; hemeoxygenase-1, superoxide dismutase, glutathione peroxidase in the prefrontal cortex (PFC), were upregulated in SD rats at PND33 but not at PND90. PFC interleukin-6 protein expression was elevated at PND33 and PND90. PFC mitogen activated protein kinase phosphatase-1 (MKP-1) and p-38 protein expression were upregulated at PND90. PFC expression of glutamate receptor subunits, post synaptic density protein (PSD-95), calcium/calmodulin-dependent protein kinase (CaMKII), and extracellular signal-regulated kinase (ERK_1/2), were significantly reduced in SD rats at PND33 and PND90. PFC brain derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB) were reduced in SD rats at PND90. Our postulation is that SD by increasing PFC oxido-inflammation, negatively affects glutamate receptor subunits and PSD95 expression, which disrupts synapse formation and maturation, potentially causing anxiety-like behavior at PND33. Oxido-inflammation further results in MKP-1 and CaMKII-mediated blockade of ERK_1/2 activation, which inhibits CREB dependent BDNF expression. This most likely disrupts neuronal circuit development, leading to depression-like behavior at PND90.