Group I metabotropic glutamate receptors contribute to the antiepileptic effect of electrical stimulation in hippocampal CA1 pyramidal neurons.
Autor: | Ghasemi Z; Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada., Naderi N; Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Shojaei A; Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Raoufy MR; Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Ahmadirad N; Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran., Barkley V; Krembil Research Institute, University Health Network, Toronto, Canada., Mirnajafi-Zadeh J; Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Institute for Brain Sciences and Cognition, Tarbiat Modares University, Tehran, Iran. Electronic address: mirnajaf@modares.ac.ir. |
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Jazyk: | angličtina |
Zdroj: | Epilepsy research [Epilepsy Res] 2021 Dec; Vol. 178, pp. 106821. Date of Electronic Publication: 2021 Nov 19. |
DOI: | 10.1016/j.eplepsyres.2021.106821 |
Abstrakt: | Low-frequency deep brain stimulation (LFS) inhibits neuronal hyperexcitability during epilepsy. Accordingly, the use of LFS as a treatment method for patients with drug-resistant epilepsy has been proposed. However, the LFS antiepileptic mechanisms are not fully understood. Here, the role of metabotropic glutamate receptors group I (mGluR I) in LFS inhibitory action on epileptiform activity (EA) was investigated. EA was induced by increasing the K + concentration in artificial cerebrospinal fluid (ACSF) up to 12 mM in hippocampal slices of male Wistar rats. LFS (1 Hz, 900 pulses) was delivered to the bundles of Schaffer collaterals at the beginning of EA. The excitability of CA1 pyramidal neurons was assayed by intracellular whole-cell recording. Applying LFS reduced the firing frequency during EA and substantially moved the membrane potential toward repolarization after a high-K + ACSF washout. In addition, LFS attenuated the EA-generated neuronal hyperexcitability. A blockade of both mGluR 1 and mGluR 5 prevented the inhibitory action of LFS on EA-generated neuronal hyperexcitability. Activation of mGluR I mimicked the LFS effects and had similar inhibitory action on excitability of CA1 pyramidal neurons following EA. However, mGluR I agonist's antiepileptic action was not as strong as LFS. The observed LFS effects were significantly attenuated in the presence of a PKC inhibitor. Altogether, the LFS' inhibitory action on neuronal hyperexcitability following EA relies, in part, on the activity of mGluR I and a PKC-related signaling pathway. (Copyright © 2021 Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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