Curtailment of sleep in modern society leads to a spectrum of neuropsychiatric disorders. However, the molecular mechanisms underlying the effects of sleep deprivation (SD) remain elusive and currently there is no effective therapy to alleviate these effects. Here, we aimed to examine SD-induced cellular and molecular alterations in mouse prefrontal cortex (PFC) and whether subchronic citalopram (CTM) treatment can negate these alterations. Three-month-old C57BL/6 J mice were divided into control (Ctrl), SD, CTM alone and CTM + SD groups. CTM and CTM + SD group mice were treated with CTM for five consecutive days at a dose of 10 mg/kg per day before the experimental procedure. SD and CTM + SD group mice were sleep-deprived for 24 h using an automated treadmill method. We found that 24 h SD causes a marked reduction in the levels of phosphorylated calcium/calmodulin kinase II (pCaMKII), phosphorylated cyclic AMP-responsive element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) in mouse PFC. Patch clamp recording of pyramidal neurons from acute PFC slices revealed that SD decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), suggesting a SD-induced postsynaptic alteration. Interestingly, subchronic CTM treatment prevents such SD-induced reductions in pCaMKII, pCREB and BDNF levels, and in mEPSC amplitude. These data suggest that CTM offers neuroprotection against SD-induced molecular and electrophysiological alterations.
Keywords: BDNF; CREB; CaMKII; Citalopram; Neuronal excitability; PFC; Sleep deprivation.
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