The PPARα Agonist Fenofibrate Reduces Prepulse Inhibition Disruption in a Neurodevelopmental Model of Schizophrenia

Abstract

Oxidative stress has been implicated in neurodevelopmental theories of schizophrenia. Antioxidant Peroxysome Proliferator-Activated Receptors α (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's t-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.

Figure 1

PPI scores (%) at PND35. PPI mean scores at PND35 are comparable between groups. No effect of factors KA or FENO is found with the two-way ANOVA.

Figure 2

PPI scores (%) at PND56. All PPI mean scores are lower in group KN than in control groups (ON and OF). PPI mean scores in group KF tend to be intermediate between control groups (ON and OF) and group KN. *P < 0.5%.