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Belokopytova K.V.,Moldova Academy of Sciences | Belov O.V.,Joint Institute for Nuclear Research | Kudrin V.S.,Zakusov Research Institute of Pharmacology | Narkevich V.B.,Zakusov Research Institute of Pharmacology | And 3 more authors.
Neurochemical Journal | Year: 2016

We studied the effect of carbon ions (12C) with an energy of 500 MeV/nucleon at a dose of 1 Gy on monoamine metabolism in the brains of rats of different ages. Neurochemical parameters that characterize the distribution of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and its metabolites were evaluated during 2 months on days 30 and 90 after the exposure to radiation. We studied the prefrontal cortex, hypothalamus, hippocampus, and striatum. The results showed changes in the activities of the NA, DA, and 5-HT systems in rats of different age groups after exposure to radiation. The most prominent differences in the exposed and control animals were observed in the prefrontal cortex and hypothalamus, which indicates the important role of these brain regions in long-term effects of exposure to radiation on the central nervous system. A comparison of animals from different age groups showed a decrease in the intensity of the temporal changes in all analyzed structures except the striatum in the exposed rats. Based on these findings, we assumed that the activation of compensatory and repairing mechanisms occurs in the late post-radiation period. At relatively low linear energy transfer of particles (10.6 keV/µm), it may lead to the partial recovery of brain functions that were impaired by radiation. At higher values of the linear energy transfer, the compensatory and recovery processes are activated to a lesser degree and functional impairment increases with time. © 2016, Pleiades Publishing, Ltd.

Belokopytova K.V.,Joint Institute for Nuclear Research | Belov O.V.,Joint Institute for Nuclear Research | Kudrin V.S.,Zakusov Research Institute of Pharmacology | Narkevich V.B.,Zakusov Research Institute of Pharmacology | And 4 more authors.
Neurochemical Journal | Year: 2015

We investigated the levels of monoamines and their metabolites in certain brain structures of rats at 30 and 90 days after exposure to carbon ions (12C) with an energy of 500 MeV/nucleon. The linear energy transfer and radiation dose were 10.6 keV/µm and 1 Gy, respectively. The concentrations of substances were measured in five structures of the brain, including the prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus, and striatum. On day 30 after the exposure, the most pronounced changes in the concentration of monoamines and their metabolites were observed in the nucleus accumbens; the smallest changes were found in the hippocampus and striatum. After 90 days, significant changes were still present in the nucleus accumbens. At the same time, these changes became less evident in other structures. A comparison of our results with the data of similar previous experiments (24 hours after exposure) showed that the most pronounced effect was observed soon after radiation exposure. The induced damage diminished at a later period. Based on the results of our study, we made the hypothesis that the change in the metabolism of monoamines may be compensated if the linear-energy transfer values were relatively low (10.6 keV/μm). At higher values of linear-energy transfer, compensatory and regenerative processes did not occur; the effect increased with time. An increased susceptibility of the nucleus accumbens was found at all the time points after the exposure, which may indicate an important role of this brain structure in the radiation-induced impairment of cognitive functions and emotional and motivational states. © 2015, Pleiades Publishing, Ltd.

Pligina K.L.,Zakusov Research Institute of Pharmacology | Zhanataev A.K.,Zakusov Research Institute of Pharmacology | Kulakova A.V.,Zakusov Research Institute of Pharmacology | Chaika Z.V.,Zakusov Research Institute of Pharmacology | Durnev A.D.,Zakusov Research Institute of Pharmacology
Russian Journal of Genetics | Year: 2016

The influence of N-acetylcysteine (ACC) on the cytogenetic effects of etoposide in F1 CBA × C57BL/6 mice was studied. Etoposide introduced intraperitoneally in doses of 10, 20, 40, and 60 mg/kg has a dose-dependent clastogenic activity and has an aneugenic effect with the induction of mainly hypohaploid oocytes. ACC significantly decreases the aneugenic and clastogenic activity of etoposide (20 mg/kg) in oocytes of 6-, 9-, and 12-week-old mice during triple introduction at a dose 200 mg/kg per os. The most pronounced anticlastogenic ACC activity (an 80% decrease) was registered in 9-week-old females; a 100% decrease in aneugenesis was detected in 6-week-old female mice. © 2016, Pleiades Publishing, Inc.

Gudasheva T.A.,Zakusov Research Institute of Pharmacology | Deeva O.A.,Zakusov Research Institute of Pharmacology | Mokrov G.V.,Zakusov Research Institute of Pharmacology | Yarkov S.A.,Zakusov Research Institute of Pharmacology | And 2 more authors.
Doklady Biochemistry and Biophysics | Year: 2015

On the basis of the structure of Alpidem, a pyrazolopyrimidine ligand of the translocator protein (TSPO), a dipeptide TSPO ligand, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), was designed and synthesized using our own original peptide design strategy. This compound exhibited anxiolytic activity in BALB/cAnN mice in the “open-field” test and in outbred CD1 mice in the “elevated plus maze” test. The stereoselectivity of the anxiolytic effect of GD-23 is demonstrated. The results of this study suggest that GD-23 is a ligand of the translocator protein, and its structure can become the basis for creating anxiolytics with a fundamentally new mechanism of action. © 2015, Pleiades Publishing, Ltd.

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