Investigation the Effects of Orexins on Behavioral, Morphological and Electrophysiological Alterations Induced by the Kainic Acid Model of Temporal Lobe Epilepsy
Journal Title: The 1st Annual Meeting of Georgian Center for Neuroscience Research - Year 2020, Vol 2, Issue 20
Abstract
Epilepsy is a chronic brain disease, which has a significant impact on the quality of life of up to 50 million people worldwide. The pathophysiology of disease is still not clear. Epilepsy is characterized by the appearance of spontaneous recurrent seizures that has been associated with dysregulation of excitatory/inhibitory synaptic transmissions. Epilepsy is associated with increased risk for many comorbid conditions including sleep disorders, cognitive impairments and psychological disease. Based on numerous studies the hypothalamic orexinergic system(OX) is involved in various physiological function and the role of this system in pathophysiology of several brain disorders such as narcolepsy and eating disorders are well documented, but data about their role in epileptogeneses is still on debate. OX neurons connected to the seizure-generating hippocampal network. The distribution of OX receptors in the hippocampus, suggests a possible importance of OX in the control of the hippocampal related functions. The aim of the present work was to study the effect of orexins on behavioral, morphological and electrophysiological alterations induced by the kainic acid model of temporal lobe epilepsy. In rats the kainite model of epilepsy were induced by single intraperitoneal injection of kainic acid (15mg/kg). Epilepsy model-associated behavioral changes were monitored in the open-field, T-maze test and passive avoidance task. A morphological analysis have done on hippocampal and hypothalamus slices of the rat brain for assuming destructive processes induced by kainic acid status epilepticus (KA-SE). In vivo electrophysiological experiments were performed to investigate the effects of intracerebroventricular application of OX (A and B) on background spiking activity and evoked field responses of the hippocampus. Bipolar intrahippocampal single and paired electrical stimulation of CA1/CA3 fields were performed in wild type and KA-SE rats. Our experiments showed that KA-SE promotes behavioral changes and induces memory disturbance, morphological analyses show reduction of main glutamatergic pyramidal neurons, which was in correlation with decrease amount of Glutamicaciddecarboxylase (GAD)-positive neurons in hippocampus and loss of OX-B positive cells in periventricular area of the hypothalamus. Electrophysiological experiment showed that OX-A decreases amplitude and increases the frequency of baseline activity in CA1, this changes were accompanied by concomitant reduction of duration of the responses. No significant changes were observed in CA3. OX-A injection increased the amplitude of single evoked responses, but it has no effect on paired pulse facilitation in CA1 showing its postsynaptic action. OX-B was ineffective, indicating involvement of OX1 receptors in the effects of OX-A. Alterations caused by kainite-model of epilepsy were different in CA1/CA3 fields and KA-SE shifts the character of influence of OX-A in CA1 field of Hippocampus.
Authors and Affiliations
Ts. Kapanadze, M. Qurasbediani, M. Chikovani, B. Chkhartishvili, N. Doreulee
Keywords
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- EP ID EP677947
- DOI 10.29088/GCNR-2020.38
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