Insulin Protects Cortical Neurons Against Glutamate Excitotoxicity
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24.09.2019 |
Krasil’nikova I.
Surin A.
Sorokina E.
Fisenko A.
Boyarkin D.
Balyasin M.
Demchenko A.
Pomytkin I.
Pinelis V.
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Frontiers in Neuroscience |
10.3389/fnins.2019.01027 |
0 |
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© 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.
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Hypoxic hemorrhagic brain lesions in neonates: The significance of determination of neurochemical markers, inflammation markers and apoptosis in the neonatal period and catamnesis follow-up results
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01.01.2018 |
Trepilets V.
Golosnaya G.
Trepilets S.
Kukushkin E.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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2 |
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© 2018, Pediatria Ltd.. All rights reserved. Objective of the research – to reveal the correlation between neurochemical criteria in the neonatal period and the consequences of severe hypoxic hemorrhagic CNS lesions in children according to catamnesis data. Materials and methods: researchers analyzed 54 cases of newborns of different gestational age (GA) that were in the ICU after birth due to severe condition; all newborns had combined hypoxic hemorrhagic brain lesion detected by neurosonography – periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH) of various severity. Catamnesis follow-up was performed up to 2–2,5 years of age. The control group consisted of 20 newborns, comparable in GA, body weight at birth, with an Apgar score of at least 6 points in the 1st minute of life and without changes in neurosonography. In the neonatal period, serum concentrations of S100, BDNF, VEGF, ALCAM, DR5 were studied in dynamics using the quantitative ELISA (Enzyme Linked Immuno Sorbent Assay) according to a standard protocol. Results: the concentration of factors contributing to destructive changes in tissues (S100, DR5, ALCAM) in the serum, was in inverse correlation with the level of VEGF and BDNF. The latter had a direct correlation relationship. VEGF directly correlated with CNTF by the end of the 2 nd week of life. Results of catamnesis follow-up: 43 children diagnosed with cerebral palsy, 25 with spastic diplegia, 18 with spastic tetraparesis, and 11 without evident motor disorders. In 28 children I–III level of motor disorders was determined according to GMFS, in 26 children – IV–V level. At the age of 2 years, all children underwent MRI of the brain and gliio-atrophic changes were detected. Significant differences in the implementation of neurological consequences were found between the number of children with grade I and II IVH and PVL and III–IV degree IVH and PVL. Conclusion: children with PVL and IVH III–IV degree have a high risk of severe neurological outcomes – spastic tetraparesis, impaired motor activity by GMFS IV–V level, mental retardation and symptomatic epilepsy.
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Late-life depression and alzheimer disease: A potential synergy of the underlying mechanisms
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01.01.2018 |
Leszek J.
Trypka E.
Koutsouraki E.
Michmizos D.
Yarla N.
Tarasov V.
Ashraf G.
Aliev G.
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Current Medicinal Chemistry |
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2 |
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© 2018 Bentham Science Publishers. A number of biological and clinical characteristics typical of late life depression (LLD) have been suggested by recent research findings. The close association of LLD with cognitive impairment is now well documented and evidenced. However, it is still not clear whether it is depression that leads to cognitive decline, and in more severe cases, to dementia. The work presented in this review article suggests that depression and dementia frequently and strongly copresent, even if the causality remains largely opaque.
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