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Effect of Anakinra on the Gene Expression of Receptors Activated by the Peroxisome Proliferator in the Rat Brain in the Lithium Pilocarpine Model of Epilepsy

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Abstract

The role of neuroinflammation in the mechanisms of epileptogenesis has been widely discussed in recent years. One of the factors influencing inflammatory processes in the brain may be changes in the expression of nuclear transcription factors, in particular peroxisome proliferator-activated receptors (PPARs). Agonists of these receptors have a pronounced neuroprotective effect in epilepsy models. Studies carried out on cells of various body tissues reveal a close functional relationship that exists between the genes of Ppars, the proinflammatory cytokine interleukin-1 (IL-1β) and the anti-inflammatory cytokine interleukin 1 receptor antagonist (IL-1ra). This work aimed to study the peculiarities of Ppars gene expression in rat brain structures in a lithium-pilocarpine model of epilepsy and to evaluate the possible effect of IL-1ra (the drug anakinra) on these parameters. Pilocarpine was administered to Wistar rats at 7–8 weeks of age, one day after LiCl injections. Anakinra was administered for one week after pilocarpine (the first injection of 100 µg/kg one hour after convulsions, then for 5 days at 100 µg/kg and 2 days at 50 µg/kg), after which brain samples were taken for biochemical analysis. Ppara, Ppard, and Pparg gene expression was assessed by reverse transcription followed by real-time polymerase chain reaction in the dorsal and ventral hippocampus, temporal cortex, and amygdala. Pilocarpine-induced seizures were shown to increase Ppard and Pparg gene expression in the ventral hippocampus and to decrease Ppara gene expression in all examined brain regions. Anakinra enhances the decrease in Ppara gene expression, has no effect on Ppard mRNA production, and levels out the increase in Pparg gene expression. Thus, Ppars gene expression in the brain changes during epileptogenesis; anakinra multidirectionally regulates Ppara and Pparg mRNA production, but has no effect on Ppard gene expression.

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Funding

Supported by RFBR, Grant no. 20-515-00020 and BRFFI, Grant no. M20R-328.

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  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    A. I. Roginskaya, A. V. Dyomina, A. A. Kovalenko, M. V. Zakharova, A. P. Schwarz & O. E. Zubareva

  2. Institute of Physiology, National Academy of Sciences of Belarus, Minsk, Belarus

    T. B. Melik-Kasumov

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Idea of work and planning of—O.E.Z., T.B.M.-K., article writing and editing—A.I.R., O.E.Z., T.B.M.-K., A.A.K., A.V.D.—data collection and processing—A.V.D., A.A.K., M.V.Z., A.P.S.

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Translated by A. Dyomina

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 4, pp. 490–504https://doi.org/10.31857/S0869813922040070.

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Roginskaya, A.I., Dyomina, A.V., Kovalenko, A.A. et al. Effect of Anakinra on the Gene Expression of Receptors Activated by the Peroxisome Proliferator in the Rat Brain in the Lithium Pilocarpine Model of Epilepsy. J Evol Biochem Phys 58, 598–609 (2022). https://doi.org/10.1134/S0022093022020260

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