The Investigation of apoptotic changes and malondialdehyde level in prefrontal cortex of rat brain in an experimental schizophrenia model and the protective effects of omega-3 fatty acids

2. ABSTRACT THE INVESTIGATION OF APOPTOTIC CHANGES AND MALONDIALDEHYDE LEVEL IN PREFRONTAL CORTEX OF RAT BRAIN IN AN EXPERIMENTAL SCHIZOPHRENIA MODEL AND THE PROTECTIVE EFFECTS OF OMEGA-3 FATTY ACIDS The anatomical, histological, and biochemical basis of the etiology of schizophrenia is unknown. However, substantial progress has been made to define its pathophysiology. Evidence has become increasingly available to support the view that some of the neuropathological changes in schizophrenia may be the result of increased free radical-mediated or reactive oxygen species mediated neuronal injury, n-3 fatty acids is an essential fatty acid found in large amount in fish oil. Addition of n-3 fatty acids to the diet together with standard neuroleptic treatment may be necessary for prevention of cellular structures of central nervous system. Primary objective of this study is to indicate the contribution effect of lipid peroxidation to the neuropathophysiology of schizophrenia, and that prevention of lipid peroxidation may improve prognosis, probably by producing improvements in the structure, and thereby also in the functions, of neuronal membranes. Healthy adult and male Wistar Albino rats were obtained Firat University Biomedical Research Unit and 30 rats divided into three groups. MK-801 was given intraperitoneally at the dose of 0.5mg/kg/day for 5 days in experimental psychosis group, n-3 fatty acid (800 mg/kg/day, Marincap® capsule) was given to treatment group for 6 days by peroral. In control group, sahne was given in thesame way. In 7 days the beginning of the experiments rats were killed by decapitation. Brain were removed and prefrontal part of the brain was divided for histological and biochemical analyses. Histological preparats were stained with HE and analyzed. Malondialdehyde (MDA) and protein carbonyl (PC) analyses were made by spectrophotometric methods. The histological examination demonstrated that MK-801 induced prefrontal apoptosis. A similar series of experiments has shown that n-3 fatty acids supplementation to the diet of rats decreased the apoptotic cell account in prefrontal cortex after MK-801 injection. Malondialdehyde, as an indicator of lipid peroxidation, as well as protein carbonyl, as an indicator of protein oxidation, levels was found to be increased significantly in prefrontal cortex of MK-801 group (pO.OOOl) compared to control group. In n-3 treated rats, prefrontal tissue malondialdehyde and protein carbonyl levels were decreased significantly when compared to MK-801 group (pO.OOOl). As a conclusion, MK-801 at the dose of 0.5 mg/kg/day may induce apoptotic changes and oxidative stress in prefrontal cortex of rats. This experimental study also provides some evidences for the protective effects of n-3 fatty acids on MK-801 -induced changes in prefrontal rat cortex. Keywords: MK-801, prefrontal cortex, apoptosis, omega-3 fatty acids, malondialdehyde, protein carbonyl. 4