Anxiety reducing in rats after cerebral ischemia and the number increasing of neuronal gap junctions in penumbra and core by carbenoxolone

Надежда Александровна Логинова; Николай Викторович Панов; Николай Степанович Косицын; Михаил Михайлович Свинов

Anxiety reducing in rats after cerebral ischemia and the number increasing of neuronal gap junctions in penumbra and core by carbenoxolone

Надежда Александровна Логинова¹, Николай Викторович Панов², Николай Степанович Косицын³, Михаил Михайлович Свинов⁴

research article Pages: 20-27

¹ к.б.н., ст. науч. сотрудник, лаборатория функциональной нейроцитологии, Институт высшей нервной деятельности и нейрофизиологии РАН (Москва)
² лаборант, лаборатория функциональной нейроцитологии, Институт высшей нервной деятельности и нейрофизиологии РАН (Москва) Анастасия Александровна Потехина (Прокуратова) - мл. науч. сотрудник, лаборатория функциональной нейроцитологии, Институт высшей нервной деятельности и нейрофизиологии РАН (Москва)
³ д.б.н., профессор, гл. науч. сотрудник, заслуженный деятель науки РФ, лаборатория функциональной нейроцитологии, Институт высшей нервной деятельности и нейрофизиологии РАН (Москва)
⁴ к.б.н., зав. лабораторией функциональной нейроцитологии, Институт высшей нервной деятельности и нейрофизиологии РАН (Москва)

Keywords: carbenoxolone connexin-36 neocortex photochemical thrombosis anxiety open field elevated plus maze rats

Abstract

In present study we have investigated the anxiety of rats after cerebral ischemia and the number of neuronal gap junctions in core, penumbra and intact zone of neocortex, where we produced ischemia by method of photochemical thrombosis. We used four groups of rats: sham rats (n=13), sham rats with i.v. injection of carbenoxolone in dose 1mg/kg (n=15), rats after cerebral ischemia (n=24) and rats with i.v. injection of carbenoxolone in dose 1mg/kg , 30 minutes after cerebral ischemia (n=25). A day before cerebral ischemia all rats were tested in open field, second test were carried out on 4th day after ischemia and on 6th day after ischemia all rats were tested in elevated plus maze. On 8th day all rats were taken for immunohistochemical analysis and we have investigated the number of neuronal gap junctions in intact zone, penumbra and core, staining their brains using immunostaining to connexin-36. The level of anxiety was increased in sham rats with carbenoxolone injection and in rats with cerebral ischemia. The number of neuronal gap junctions were decreased compared with sham group (p<0.05) in both groups. The opposite effect we have observed after carbenoxolone injection to experimental ischemic rats. Their behavior was similar to sham rats, as well as the number of gap junctions. Carbenoxolone injection to experimental ischemic rats reduced the level of anxiety and increased the number of neuronal gap junctions. We suppose that changes in behavior and in number of gap junctions may be caused by indirect impact of carbenoxolone on glucocorticoid system. The reported study was supposed by RFBR, research project No. 14-04-32121 mol_a

How to cite

Логинова Н.А., Панов Н.В., Косицын Н.С., Свинов М.М. Снижение тревожности крыс после ишемии головного мозга и увеличение числа нейрональных щелевых контактов в области пенумбры и очага инсульта при введении карбеноксолона // Биомедицинская радиоэлектроника. 2017. № 2. С. 20–27.

References

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[1] Loginova N.A., Panov N.V., Prokuratova A.A., Kosicyn N.S., Svinov M.M. Izmenenie chisla nejjronalnykh shhelevykh kontaktov pri ishemii mozga u krys // Nejjrokompjutery: razrabotka, primenenie. 2015. № 8. S. 74-80.

[2] Loginova N.A., Panov N.V., Kosicyn N.S., Prokuratova A.A., Svinov M.M. Uvelichenie kolichestva nejjronalnykh shhelevykh kontaktov pod dejjstviem vnutrivennogo vvedenija karbenoksolona pri ishemii mozga u krys // Biomedicinskaja radioehlektronika. 2015. № 4. S. 48-50.

[3] Broomfield N.M., Quinn T.J., Abdul-Rahim A.H., Walters M.R., Evan J.J. Depression and anxiety symptoms post-stroke/TIA: prevalence and associations in cross-sectional data from a regional stroke registry // BMC Neurology. 2014. V. 14. Iss. 198. http://www.biomedcentral.com/1471-2377/14/198

[4] de Pina-Benabou M.H., Szostak V., Kyrozis A., Rempe D., Uziel D., Urban-Maldonado M., Benabou S., Spray D.C., Federoff H.J., Stanton P.K., Rozental R. Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia // Stroke. 2005. V. 36. P. 2232-2237.

[5] Holmes M.C., Seckl J.R. The role of 11β-hydroxysteroid dehydrogenases in the brain // Molecular and Cellular Endocrinology. 2006. V. 248. Iss. 1-2. P. 9-14.

[6] Juszczak G.R., Sqiergiel A.H. Properties of gap junction blockers and their behavioural, cognitive and electrophysiological effects: Animal and human studies // Progress in neuro-psychopharmacology and biological psychiatry. 2009. V. 33. P. 181-198.

[7] Juszczak G.R., Swiergiel A.H. Behavioral pharmacology of gap junctions / Gap junctions in the brain. Ed. By Ekrem Dere. Elsevier. 2013. P. 261-276.

[8] Oguro K., Jover T., Tanaka H., Lin Y., Kojima T., Oguro N., Grooms S.Y., Bennett M.V.L., Zukin S. Global ischemia-induced increases in the gap junctional proteins connexin 32 (C×32) and C×36 in hippocampus and enhanced vulnerability of C×32 knock-out mice // The journal of neuroscience. 2001. V. 21. Iss. 19. P. 7534-7542.

[9] Samarasinghe R.A., Witchell S.F., DeFranco D.B. Cooperativity and complementarity: synergies in non-classical and classical glucocorticoid signaling // Cell Cycle. 2012. V. 11. № 15. P. 2819-2827.

[10] Sapolsky R.M., Pulsinelli W.A. Glucocorticoids potentiate ischemic injury to neurons: therapeutic implications // Science. 1985. V. 229. Iss. 4720. P. 1397-1400.

[11] Schoenfeld T.J., Kloth A.D., Hsueh B., Runkle M.B., Kane G.A., Wang S., Gould E. Gap junctions in the ventral hippocampal-medial prefrontal pathway are involved in anxiety regulation // The Journal of Neuroscience. 2014. V. 34. № 47. P. 15679-15688.

[12] Sun J-D., Liu Y., Yuan Y-H., Li J., Chen N-H. Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats // Neuropsychopharmacology. 2012. V. 37. P. 1305-1320.

[13] Vivek Sagar G.D., Larson D.M. Carbenoxolone inhibits junctional transfer and upregulates connexin43 expression by a protein kinase A-dependent pathway // Journal of Cellular Biochemistry. 2006. V. 98. Iss. 6. P. 1543-1551.

[14] Walf A.A., Frye Ch.A. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents // Nature protocols. 2007. V. 2. P. 322-328.

[15] Winter B., Juckel G., Viktorov I., Katchanov J., Gietz A., Sohr R., Balkaya M., Hortnagl H., Endres M. Anxious and hyperactive phenotype following brief ischemic episodes in mice // Biological Psychiatry. 2005. V. 57. Iss. 10. P. 1166-1175.

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