Репозиторий Университета

© Copyright © 2019 Krasil’nikova, Surin, Sorokina, Fisenko, Boyarkin, Balyasin, Demchenko, Pomytkin and Pinelis. Glutamate excitotoxicity is implicated in the pathogenesis of numerous diseases, such as stroke, traumatic brain injury, and Alzheimer’s disease, for which insulin resistance is a concomitant condition, and intranasal insulin treatment is believed to be a promising therapy. Excitotoxicity is initiated primarily by the sustained stimulation of ionotropic glutamate receptors and leads to a rise in intracellular Ca2+ ([Ca2+]i), followed by a cascade of intracellular events, such as delayed calcium deregulation (DCD), mitochondrial depolarization, adenosine triphosphate (ATP) depletion that collectively end in cell death. Therefore, cross-talk between insulin and glutamate signaling in excitotoxicity is of particular interest for research. In the present study, we investigated the effects of short-term insulin exposure on the dynamics of [Ca2+]i and mitochondrial potential in cultured rat cortical neurons during glutamate excitotoxicity. We found that insulin ameliorated the glutamate-evoked rise of [Ca2+]i and prevented the onset of DCD, the postulated point-of-no-return in excitotoxicity. Additionally, insulin significantly improved the glutamate-induced drop in mitochondrial potential, ATP depletion, and depletion of brain-derived neurotrophic factor (BDNF), which is a critical neuroprotector in excitotoxicity. Also, insulin improved oxygen consumption rates, maximal respiration, and spare respiratory capacity in neurons exposed to glutamate, as well as the viability of cells in the MTT assay. In conclusion, the short-term insulin exposure in our experiments was evidently a protective treatment against excitotoxicity, in a sharp contrast to chronic insulin exposure causal to neuronal insulin resistance, the adverse factor in excitotoxicity.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Objectives. To study the expression of various neurotransmitter transporters (glutamate, aspartate, lactate, choline) in cultures of astrocytes from different part of the brain (cortex, hippocampus, and brainstem) in rats aged three and 11 days. Materials and methods. An experimental study was performed using 24 Rattus norvegicus rats aged three (n = 12) and 11 days (n = 12). High-throughput sequencing results were analyzed. Results. Expression of the glutamate and aspartate transporters in the brainstem in three-day-old rats was greater than in other areas, though the reverse pattern was seen in rats aged 11 days. Expression of the lactate transporter with age was identical to that in the cortex. Conclusions. The data obtained here demonstrated the nature of neuroastrocyte relationships and the role of astrocytes in the process of signal transmission. The results of the study, carried out using original methods of investigating neurotransmitter transporters, allow them to be recommended for monitoring the processes of neurogenesis and neurohomeostasis, including in cerebrovascular and neurodegenerative diseases.

© 2018 Izdatel'stvo Meditsina. All rights reserved. NMDA receptor modulators are a new class of antidepressants with rapid onset of action and lasting antidepressant effect. These drugs increase BDNF level in CNS and adult hippocampal neurogenesis, which events are in common for both NMDA receptor modulators and classical antidepressants. However, unlike classical antidepressants, drugs of this new group produce no direct influence on the monoaminergic system, but regulate the neuroplasticity in the prefrontal cortex and hippocampus via modulation of the glutamatergic neurotransmission. Clinical tests of ketamine and rapastinel confirmed the rapid onset of action and the continuation of stable antidepressant effect (upon single administration per 7 days) for both usual and treatment-resistant forms of depression.

© Team of authors, 2018. Objective. To investigate the expression of transporters of different neurotransmitters (glutamate, aspartate, lactate, choline) in the culture of astrocytes isolated from different regions of the brain (cortex, hippocampus and brainstem) in 3- and 11-day rats. Material and methods. An experimental study was performed on 24 3-(n=12) and 11-days (n=12) old rats (Rattus norvegicus). The results of high-performance sequencing were analyzed. Results. The expression of glutamate and aspartate transporters in the brainstem of 3-day rats was higher than in other regions, however, an opposite effect was observed in 11-day rats. The expression of lactate transporters with age became identical to those of the cortex. Conclusion. The data demonstrate the particular qualities of neuro-astrocytic connections and the important role of astrocytes in signal transmission. Results of the study performed by using genetic methods developed by the authors for the study of neurotransmitter transporters make it possible to recommend these methods to control the neurogenesis and neurohomeostasis, including in cerebrovascular and neurodegenerative diseases.