The PPARαAgonist Fenofibrate Reduces Prepulse InhibitionDisruption in a Neurodevelopmental Model of Schizophrenia

[摘要] Oxidative stress has been implicated in neurodevelopmental theories of schizophrenia. Antioxidant Peroxysome Proliferator-Activated Receptorsα(PPARα)agonist fenofibrate has neuroprotective properties and could reverse early preclinical infringements that could trigger the illness. We have evaluated the neuroprotective interest of fenofibrate in a neurodevelopmental rat model of schizophrenia. The oxidative lesion induced by Kainic Acid (KA) injection at postnatal day (PND) 7 has previously been reported to disrupt Prepulse Inhibition (PPI) at PND56 but not at PND35.In 4 groups of 15 male rats each, KN (KA-PND7+normal postweaning food), KF (KA-PND7+fenofibrate 0.2% food), ON (saline-PND7+normal food), and OF (saline+fenofibrate food), PPI was recorded at PND35 and PND56. Three levels of prepulse were used: 73 dB, 76 dB, and 82 dB for a pulse at 120 dB. Four PPI scores were analyzed: PPI73, PPI76, PPI82, and mean PPI (PPIm). Two-way ANOVAs were used to evaluate the effects of both factors (KA+fenofibrate), and, in case of significant results, intergroup Student’st-tests were performed. We notably found a significant difference (P<0.05) in PPIm between groups KN and KF at PND56, which supposes that fenofibrate could be worthy of interest for early neuroprotection in schizophrenia.

[学科分类] 精神健康和精神病学