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.
Highlights
Schizophrenia is a chronic and severe mental illness that affects around 1% of the population and is characterized by delusions, hallucinations, and thought disorder [1]
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
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
Summary
Schizophrenia is a chronic and severe mental illness that affects around 1% of the population and is characterized by delusions, hallucinations, and thought disorder [1]. Two different types of pathophysiological processes have been suggested to underlie schizophrenia: neurodegeneration and neurodevelopmental disruption [2]. Neurodegenerative models suppose that lesional mechanisms and neuronal death are continuous, which could underlie some progressive deficits observed during the course of the illness [3]. Neurodevelopmental models suppose that some early neuronal infringements could disrupt the normal course of the cerebral development, leading to prodromal abnormalities and much later to the occurrence of the first clinical symptoms, which will sign the onset of the illness [4]. Neuroprotective therapeutics should be quickly applied after the onset of the illness in order to limit the extension of lesions and the aggravation of symptoms and deficits [5]. Neuroprotective strategies could be envisaged during or between the initial infringement and the occurrence of symptoms, which could limit the long-term symptom burden or even prevent the outcome of the illness
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