Extracellular Alkalosis Reduces the Neurotoxicity of Zinc Ions in Cultured Cerebellar Granule Neurons.

Autor: Shedenkova MO; M.V. Lomonosov Moscow State University, Leninskiye gory, 119234, Moscow, Russia.; Research Center of Neurology, Moscow, Russia., Stelmashook EV; Research Center of Neurology, Moscow, Russia., Golyshev SA; M.V. Lomonosov Moscow State University, Leninskiye gory, 119234, Moscow, Russia., Genrikhs EE; Research Center of Neurology, Moscow, Russia., Isaev NK; M.V. Lomonosov Moscow State University, Leninskiye gory, 119234, Moscow, Russia. nsaev61@mail.ru.; Research Center of Neurology, Moscow, Russia. nsaev61@mail.ru.
Jazyk: angličtina
Zdroj: Biological trace element research [Biol Trace Elem Res] 2023 Feb; Vol. 201 (2), pp. 856-864. Date of Electronic Publication: 2022 Jun 03.
DOI: 10.1007/s12011-022-03214-6
Abstrakt: Zn 2+ is known to be important for the normal brain functions. Disruption of zinc homeostasis and zinc-induced neurotoxicity has been shown to play a role in the development of neurodegenerative diseases. In this work, we investigated the effect of extracellular alkalosis on the zinc ions neurotoxicity in the cultured rat cerebellar granule neurons. Zinc chloride (0.03-0.06 mM, 24 h) added to the culture medium of rat cerebellar granule neurons caused the dose-dependent death of these cells. According to ultrastructural morphological features, the process of cell death could be attributed to necrosis, since it was accompanied by swelling of intracellular organelles and disruption of cell membranes against the background of relatively intact nuclear membranes. Neuronal death was associated with an increase in the level of intracellular free zinc. The toxic effect of zinc ions was significantly decreased when ionotropic glutamate NMDA-receptors were blocked by MK-801 or when the extracellular pH was increased from 7.3 to 7.8, due to a decrease in the zinc overload of the cytoplasm of these cells. The presented results demonstrate that NMDA channels are one of the Zn ion entry pathways in the cultured cerebellar granule neurons. Extracellular alkalosis reduces the zinc overload of the cytoplasm and, consequently, promotes the survival of neurons. Probably, zinc's neurotoxicity is inextricably linked with changes in the intracellular concentration of protons.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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