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Activation of the Cannabinoid Receptors Suppresses Hyperexcitation of Rat Hippocampal Neuronal Networks In Vitro

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract—

Cannabinoid receptors (CBRs) play a key role in various physiological processes, including neurogenesis, synaptic plasticity, immune modulation, cell apoptosis, metabolism regulation, cardiovascular and reproductive systems activity. Since activation of CBRs suppresses hyperexcitation and protects cells from death, their modulation may have therapeutic prospects in the treatment of such pathologies of the nervous system as mental disorders, epilepsy, Parkinson’s and Huntington’s disease, multiple sclerosis, spinal cord and brain injuries. This paper presents experimental data on the effects of the cannabinoid receptor agonist WIN 55,212-2 on the induced oscillations of intracellular Ca2+ concentration ([Ca2+]i) in two in vitro models of epileptiform activity. To study the neuroprotective properties of WIN 55,212-2, hyperexcitation was induced by the application of a GABA(A) receptor antagonist, bicuculline, or depolarizing doses of ammonium chloride. As experiments have shown, WIN 55,212-2 at a concentration of 100 nM and above significantly suppresses the [Ca2+]i oscillations frequency and reduces the basal [Ca2+]i level. At the same time, the amplitude of calcium oscillations also decreased in the presence of the agonist. WIN 55,212-2 at a concentration of 2 μM suppressed NH4Cl-induced [Ca2+]i oscillations in all neurons but caused a transient biphasic increase in the basal [Ca2+]i level in 20% of astrocytes. Thus, in this work, using various models of hyperexcitation of neuronal networks, we have demonstrated a potential antiepileptic effect of the cannabinoid receptor agonist WIN 55,212-2.

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Funding

The work was carried out within the framework of the state assignment of ICB RAS, no. 122041300005-4 “Functioning of receptors, ion channels and intracellular signaling systems, mechanisms of intercellular communications in different cell types in health and disease. Potential targets for pharmacotherapy. "

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Authors and Affiliations

  1. Institute of Cell Biophysics RAS, FRC PSCBR RAS, 142290, Pushchino, Moscow oblast, Russia

    S. A. Maiorov, S. G. Gaidin, A. M. Kosenkov & V. P. Zinchenko

  2. Al-Farabi Kazakh National University, 050040, Almaty, Republic of Kazakhstan

    B. K. Kairat

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  1. S. A. Maiorov
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  3. S. G. Gaidin
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Correspondence to V. P. Zinchenko.

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The authors declare that they have no conflict of interest.

All experiments in this study were carried out in accordance with Directive 2010/63/EU of the European Parliament and of the Council of the European Union of 22 September 2010 on the protection of animals used for scientific purposes.

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Translated by S. Gaidin

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Maiorov, S.A., Kairat, B.K., Gaidin, S.G. et al. Activation of the Cannabinoid Receptors Suppresses Hyperexcitation of Rat Hippocampal Neuronal Networks In Vitro. Biochem. Moscow Suppl. Ser. A 17, 169–175 (2023). https://doi.org/10.1134/S1990747823030078

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  • DOI: https://doi.org/10.1134/S1990747823030078

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