Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation.

INTRODUCTION: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA) inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard. METHODS: Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R) blocking administered in CSF. RESULTS: We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867) and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity. DISCUSSION: It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process.

Prenatal stress decreases spatial learning and memory retrieval of the adult male offspring of rats.

INTRODUCTION: Early life or prenatal stress induces many lifelong, mostly cognitive, homeostatic alterations in the behavior of the offspring. PURPOSE: We investigated the effect of heterogeneous sequential stress (HSS) at three separate periods, before and during the first and second half of pregnancies on spatial learning and memory retrieval of adult male offspring. METHOD: HSS is composed of several stressors, each in a day, during nine consecutive days including; restraint, swimming, isolation, and water and food deprivation on Wistar rats. The offspring were studied in a Morris water maze (MWM) apparatus to explore the latency, distance, proximity and target to opposite area as measures of learning and memory. Serum corticosterone was measured as a criterion of stress application. RESULTS: HSS increased blood corticosterone in dams of PS2 (Pregnancy Stress second half), and also in adult male offspring from BPS (Before Pregnancy Stress) and PS1 (Pregnancy Stress first half) groups. The weight of the offspring decreased in the PS1 and PS2 groups. While distance traveled and latency to locate the hidden platform were increased in BPS and PS1 acquisition trials, swimming speed was unchanged during the acquisition and retrieval tests. Moreover, time to platform location was increased in BPS and PS1 during retention tests. While control rats spent more time in the target quadrant, stressed animals spent a longer duration in the opposite quadrant. Furthermore, proximity measure was increased in all stress treated rats. CONCLUSION: It is concluded that prenatal stress, around the beginning of the pregnancy, increases corticosterone in adult male offspring, which might be the basis for spatial learning and memory retrieval deficits in this study.

Role of Oxidative Stress in Ethanol-induced Neurotoxicity in the Developing Cerebellum.

OBJECTIVE(S): The purpose of this study was to investigate the role of oxidative stress in Purkinje cell neurotoxicity of ethanol-treated rat. MATERIALS AND METHODS: Male rat pups 4-day-old was used in this study. Ethanol was administered to rat pups at a dose of 6 g/kg from postnatal days (PDs) 4 to 5. Pups were killed 90 min after the second alcohol treatment on PD 5 by decapitation and the brain was immediately removed. The cerebellum was dissected for analyzing the oxidative stress parameters and histological study. The activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in vermis of cerebellum were assayed. Thiobarbituric acid reactive substances (TBARS) levels were also measured as a marker of lipid peroxidation. RESULTS: Administration of ethanol significantly increased TBARS levels in the cerebellum compared to control pups (P< 0.01). The treated pups with ethanol exhibited a marked decrease in the GPx activity (P< 0.01) whereas, in spite of decrease in the activities of SOD and CAT, when compared to control, there were not significant differences. The spherical cell bodies of Purkinje cells in control rats are aligned nicely between the granular and molecular layers. In ethanol treated pups, Purkinje cells scattered within the Purkinje cell layer and shrinkage of the cell somata is seen. CONCLUSION: The results of the present work demonstrated that ethanol exposure during the vulnerable window could increase TBARS levels (lipid peroxidation) and decrease GPx levels in pup's cerebellum. Also, the results confirmed ethanol-induced microencephaly, cerebellar Purkinje cell loss. These findings suggest that Purkinje cell loss is, in part through decrease in the activity of GPx and increase of lipid peroxidation in the rat cerebellum.