Proteomic profiling of brain steroid 5 alpha reductases in sleep-deprivated rats

Steroid 5 alpha reductase (SR) is rate-limiting enzyme of one of two major metabolic pathways in brain steroidogenesis. Recent evidence indicates that neuroactive steroids may involved in pathogenesis of schizophrenia spectrum disorders. Moreover, SR inhibition has been shown to induce therapeutic effects in animal models of schizophrenia and in several disorders associated to dopaminergic hyperreactivity. In rodents, sleep deprivation (SD) is known to induce a series of behavioural patterns, including sensory-motor gating deficit, which might be reflective of psychosis and mania and are countered by antipsychotics. The aim of this study was to evaluate, the impact of SD on expression levels of SR isozymes in rat brain. After 72 h of SD, rats were sacrificed and brain areas dissected out. Quantitative 1D and 2D western blotting (WB) with antibodies were performed on four brain areas of both control group and SD group (n = 8 each): medial prefrontal cortex (mPFC), nucleus accumbens (nACC), ippocampus (IPPO) and amigdala (AMG). 1D and 2D WB revealed that the expression of SR-1 and SR-2 was significantly augmented in SD animals in comparison to controls (p < 0.05) in mPFC and nACC area. In IPPO and AMG expression of SR-1 and SR-2 was unchanged in SD animals in comparison to controls. Regarding therapeutic effect of SR inhibition on gating deficit, data suggest that SR increase might cause altered balancing in neurosteroid levels, and it could be responsible of behavioral disruption observed in SD animals.