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

Abstract EN

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.