Effects of Orexin on In Vivo and In Vitro Models of Epilepsy

Author: Tsira Kapanadze
Keywords: Epilepsy, Orexin, Hippocampus
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Epilepsy is most frequent chronic pathologies of the brain among neurodegenerative diseases. The abnormal electrical activity of neurons in epileptic seizures is associated with an imbalance between excitatory and inhibitory transmission (Staley, 2015). Epilepsy is a rather complex disease that is characterized by a number of potential clinical manifestations and various etiologies. Every year, approximately 2.4 million people worldwide are diagnosed with epilepsy. In high income countries new cases range between 30 and 50 per 100,000 people each year. In low and medium income countries, this number can be doubled(Singh & Trevick, 2016). The balance of cellular excitability can be affected by changes in the levels of glutamate and gamma-amino butyric acid (GABA) (Akyuz et al., 2021). The studies have covered the modulating effect of the neuropeptide orexin on glutamatergic, GABAergic and noradrenergic transmission of the hippocampus, and thus, on functions associated with the hippocampus such as long-term neuroplasticity, learning, and memory(Selbach et al., 2004; Yang et al., 2013). The orexinergic system is involved in multiple physiological processes: it regulates energy metabolism and homeostasis (Sakurai, 2003), affects the work of the cardiovascular, neuroendocrine, and gastrointestinal systems (Mondal et al., 2000), and is also involved in regulating the circadian rhythm and the sleep-wake cycle(Inutsuka & Yamanaka, 2013; Li et al., 2017). The orexinergic system is also involved in the pathogenesis of many neurodegenerative disorders, and also, is an interesting/attractive target for treatment of several diseases (Berhe et al., 2020). However, the controversial data is found in literature on the role of orexin in epileptogenesis. Several studies have shown as antiepileptic (Doreulee et al., 2009; Rejdak et al., 2009; Doreulee et al., 2010; Zhao et al., 2014) as proepileptic (Erken et al., 2012; Kortunay et al., 2012; Roundtree et al., 2016) effects of orexin. The study's objective was to assess orexin's effects during epileptiform discharges that were triggered by intrahippocampal electrical stimulation using both in vitro and in vivo electrophysiological experiments. According to the obtained results, we can summarize that neuropeptide orexin-A in pathological condition such as bicuculline model of epilepsy causes long-lasting depression of amplitude and duration of multiple discharges of pop-spikes and inhibition of spontaneous epileptiform discharges in CA-1. In addition orexin-A modulates activity of bursting neurons in CA-3 of hippocampus. Intracerebroventricular injection and cortical application of orexin (1 nM) in an in vivo experiment reduces the amount of certain amplitude discharges and spontaneous epileptic activity, but does not alter the duration of epileptiform discharges induced by electrical stimulation in the hippocampus. Our experiment's findings suggest that the orexinergic system may have an anti-epileptic effect.