ABSTRACT
Neuropeptides play an important role in the pathogenesis of epilepsy. In the present study, the effect of nesfatin1, a neuropeptide, was investigated on penicillininduced epilepsy model. Epileptiform activity was induced by an injection of penicillin into the somatomotor cortex at 56 albino Wistar rats. Nesfatin1 (i.c.v.) was administered at five different doses (12.5, 25, 50, 100, and 200 pmol) 30 min after a penicillin administration. Astressin 2B, a corticotropinreleasing factor (CRF) receptor antagonist, was administered 10 minutes later the effective dose of nesfatin1 (50 pmol, i.c.v.). Superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) levels in cerebrum were analysed by ELISA method. Nesfatin1, at the doses of 25, 50 and 100 pmol, significantly reduced the frequency of epileptiform activity. However, none of the doses of nesfatin1 had any effect on the amplitude of epileptiform activity. Astressin 2B alone did not show any effect on epileptiform activity. In addition, astressin 2B had no effect on the anticonvulsant effect of nesfatin1. Nesfatin1 (at the doses of 25, 50, 100 pmol) did not alter SOD and GSH levels, but significantly increased the GPx and GR levels. Nesfatin1 (at a dose of 50 pmol) significantly decreased the MDA level in the cerebrum. Nesfatin1 shows anticonvulsant effect and astressin 2B did not affect the anticonvulsant effect of nesfatin1. We suggest that nesfatin1 has oxidative stressmediated anticonvulsant effect in the penicillininduced epileptic activity.
Subject(s)
Anticonvulsants , Epilepsy , Rats , Animals , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Epilepsy/chemically induced , Epilepsy/drug therapy , Rats, Wistar , Superoxide Dismutase/metabolism , Oxidative Stress , Glutathione Peroxidase/metabolism , Glutathione/metabolism , Penicillins/pharmacologyABSTRACT
BACKGROUND: Caffeine (Cf) antagonizes the adenosine receptors and has neuroprotective properties. The effect of Cf has been seen on stress-induced deficits of cognitive. In this study, we have investigated the effect of Cf on learning and memory functions induced by social isolation (SI) stress. MATERIALS AND METHODS: In the present study, 21-day-old Wistar albino male rats (n = 28) were divided into four groups: the control (C), the SI, the Cf, and the social isolation + caffeine (SICf). Cf (0.3 g/L) was added to the drinking water of the experimental animals for 4 weeks. The learning and memory functions were assessed using the Morris Water Maze Test (MWMT). Following, was performed histopathological evaluation and determined hippocampal gene expression levels by RT-qPCR. RESULTS: According to MWMT findings, the time spent in the quadrant where the platform removed was decreased in the SI group compared with the C (p < 0.05). Histological evaluation showed morphological changes in SI by irregular appearance, cellular edema, and dark pycnotic appearance of nuclei in some neurons. However, it was observed that the histological structure of most of the neurons in the SICf group was similar to the C and Cf groups. Hippocampal SNAP25 expression was decreased in the Cf and SICf groups than in the C group (p < 0.05). The GFAP expression was increased in the SICf group than in the C group (p < 0.05). NR2A increased in the SI and SICf groups compared with C and Cf groups (p < 0.05). NR2B expression decreased in the Cf group compared with C and SI groups (p < 0.05). CONCLUSIONS: SI impaired spatial memory and causes morphological changes in adolescent rats, but this effect of isolation was not seen in Cf-treated animals. The effects of SI on NR2A, Cf on NR2B, and SNAP25 are remarkable. Here, we propose that the impaired effect of SI on spatial memory may be mediated by NR2A, but further studies are needed to explain this effect.