Rolland Benjamin, Marche Kevin, Cottencin Olivier, Bordet Régis
Département de Pharmacologie Médicale, EA 1046, Université Lille Nord de France, 1 place de Verdun, 59000 Lille, France.
Schizophr Res Treatment. 2012;2012:839853. doi: 10.1155/2012/839853. Epub 2012 May 15.
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.
氧化应激与精神分裂症的神经发育理论有关。抗氧化剂过氧化物酶体增殖物激活受体α（PPARα）激动剂非诺贝特具有神经保护特性，可逆转可能引发该疾病的早期临床前损害。我们评估了非诺贝特在精神分裂症神经发育大鼠模型中的神经保护作用。先前有报道称，在出生后第7天（PND7）注射 kainic 酸（KA）所诱导的氧化损伤会破坏PND56时的前脉冲抑制（PPI），但不会破坏PND35时的PPI。在4组每组15只雄性大鼠中，KN组（PND7注射KA + 正常断奶后食物）、KF组（PND7注射KA + 0.2%非诺贝特食物）、ON组（PND7注射生理盐水 + 正常食物）和OF组（生理盐水 + 非诺贝特食物），在PND35和PND56记录PPI。使用了三个前脉冲水平：120dB的脉冲对应73dB、76dB和82dB。分析了四个PPI分数：PPI73、PPI76、PPI82和平均PPI（PPIm）。使用双向方差分析来评估两个因素（KA + 非诺贝特）的影响，若结果显著，则进行组间学生t检验。我们特别发现，在PND56时，KN组和KF组之间的PPIm存在显著差异（P < 0.05），这表明非诺贝特可能对精神分裂症的早期神经保护具有重要意义。
