title: 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.
authors.affiliation: Département de Pharmacologie Médicale, EA 1046, Université Lille Nord de France, 1 place de Verdun, 59000 Lille, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rolland
authors.forename: Kevin
authors.initials: K
authors.lastname: Marche
authors.forename: Olivier
authors.initials: O
authors.lastname: Cottencin
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet