Effect of Pinealon on Learning and Expression of NMDA Receptor Subunit Genes in the Hippocampus of Rats with Experimenta
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RIMENTAL ARTICLES
Effect of Pinealon on Learning and Expression of NMDA Receptor Subunit Genes in the Hippocampus of Rats with Experimental Diabetes G. V. Karantysha, 1, M. P. Fomenkoa, A. M. Menzheritskiia, c, V. N. Prokof’eva, G. A. Ryzhakb, and E. V. Butenkoa aSouthern
b
Federal University, Rostov-on-Don, Russia St. Petersburg Institute of Bioregulation and Gerontology, St. Petersburg, Russia c Don State Technical University, Rostov-on-Don, Russia Received July 3, 2019; revised October 13, 2019; accepted November 6, 2019
Abstract—We studied the effect of the peptide drug pinealon (Glu-Asp-Arg) at doses of 50, 100, and 200 ng/kg on the training of rats in the Morris maze and the maintenance of the acquired skill after the development of experimental diabetes. We also studied the changes in the subunit composition of NMDA receptors in the hippocampus in these experimental models. In the Morris water maze, spatial learning was evaluated for 3 days, and pinealon was administered for 5 days following animal training. After training, animals were injected once with streptozotocin at a dose of 50 mg/kg of rat body weight. Estimation of the maintenance of the acquired skill and molecular studies (using real-time PCR) were performed on day 21 after modeling of experimental diabetes. It was shown that pinealon has a dose-dependent effect on the parameters studied. The most positive effect on the maintenance of the developed skill during streptozotocin-induced diabetes was observed after pinealon administration at a dose of 100 ng/kg. At this dose, we observed the smallest changes in the expression level of the Grin1, Grin2b, and Grin2d genes relative to the control values, as well as increased values of Grin2a/Grin2b ratio compared to diabetic groups treated with pinealon at dosages of 50 or 200 ng/kg. Keywords: experimental diabetes, spatial learning, NMDA receptors, real-time PCR, hippocampus, pinealon DOI: 10.1134/S181971242003006X
INTRODUCTION Diabetes mellitus is a socially significant disease, whose prevalence continues to grow, especially in developed countries [1]. The mechanisms that underlie diabetes and the role of insulin in its development are widely described in the literature. Most studies on insulin analyze its peripheral functions. However, recently the mechanisms associated with the role of insulin in the central nervous system, primarily with neuronal plasticity, have been actively investigated. It was found that insulin is able to influence the intensity of free radical processes, different types of glutamate receptors, apoptosis, the activity of proapoptotic proteases, etc. [2]. It was traditionally believed that insulin is not able to penetrate the blood-brain barrier (BBB) but is produced in situ in a number of brain regions [3], including the pituitary gland [4]. It was found that the nuclei of the hypothalamus, amygdala, hippocampus, and neocortex express insulin receptors and insulin recep1 Corresponding
author; address: ul. B. Sadovaya 105/42, Rostov-on-Don, 344006 Russia; e-mail: karantyshg
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