Background: Steroid 5a reductase (S5 R) is ratelimiting 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, 5 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, by using proteomics approaches, the impact of SD on expression levels of 5 R isozymes in rat brain Methods: After 72 h of SD, rats were sacrificed and brain areas dissected. 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 (IC) and amigdala (AM). Statistical significance for the differences in the optical density of the protein bands/spots were calculated using Student’s t-tests Results: 1D WB revealed that the expression of 5 R-1 and 5 R-2 was significantly augmented in SDa nimals in comparison to controls (p < 0.05) in mPFC and nACC area. These effects were confirmed by the analysis of 2D WB. In IP and AM expression of 5 R-1 and 5 R-2 was unchanged in SD animals in comparison to controls Conclusion: Present study shows that SD induce significant increases in the expression of 5 R-1 and 2 in the dopaminergic areas NAcc and mPFC, while no increase is noted in other two areas. Regarding therapeutic effect of 5 R inhibition on gating deficit, our data suggest that 5 R increase might cause altered balancing in neurosteroid levels, and it could be responsible of behavioral disruption observed in SD animals.
Immunoproteomic profiling of brain steroid 5 alpha reductases in sleep-deprivated rats / A. Soggiu, M. Bortolato, C. Piras, P. Devoto, L. Bonizzi, P. Roncada. ((Intervento presentato al 10. convegno Human proteome organisation annual world congress tenutosi a Ginevra nel 2011.
|Titolo:||Immunoproteomic profiling of brain steroid 5 alpha reductases in sleep-deprivated rats|
SOGGIU, ALESSIO (Primo)
BONIZZI, LUIGI (Penultimo)
RONCADA, PAOLA (Ultimo)
|Data di pubblicazione:||2011|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Enti collegati al convegno:||Human proteome organisation|
|Citazione:||Immunoproteomic profiling of brain steroid 5 alpha reductases in sleep-deprivated rats / A. Soggiu, M. Bortolato, C. Piras, P. Devoto, L. Bonizzi, P. Roncada. ((Intervento presentato al 10. convegno Human proteome organisation annual world congress tenutosi a Ginevra nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|