期刊
NEUROSCIENCE
卷 442, 期 -, 页码 202-215出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2020.07.009
关键词
Na+/K+-pump; oxidative stress; chronic unpredictable stress; aldehyde dehydrogenase 2; ischemia; spreading depolarization
资金
- Canadian Institutes of Health Research [PJT 153013]
- Heart and Stroke Foundation of Canada [G-19-0024266]
- Natural Sciences and Engineering Research Council of Canada [RGPIN/04624-2017]
The Na+/K+-ATPase is a transmembrane ion pump that has a critical homeostatic role within every mammalian cell; however, it is vulnerable to the effects of increased oxidative stress. Understanding how expression of this transporter is influenced by oxidative stress may yield insight into its role in the pathophysiology of neurological and neuropsychiatric diseases. In this study we investigated whether increased oxidative stress could influence Na+/K+-ATPase expression in various brain regions of mice. We utilized two different models of oxidative stress: a behavioural chronic unpredictable stress protocol and the Aldh2(-/-) mouse model of oxidative stress-based and age-related cognitive impairment. We identified distinct regional baseline mRNA and protein expression patterns of the Na+/K+-ATPase alpha 1 and alpha 3 isoforms within the neocortex, hippocampus, and brainstem of wildtype mice. Consistent with previous studies, there was a higher proportion of alpha 3 expression rel-ative to alpha 1 in the brainstem versus neocortex, but a higher proportion of alpha 1 expression relative to alpha 3 in the neocortex versus the brainstem. The hippocampus had similar expression levels of both alpha 1 and alpha 3. Despite increased staining for oxidative stress in higher brain, no differences in alpha 1 or alpha 3 expression were noted in Aldh2(-/-) mice versus wildtype, or in mice exposed to a 28-day chronic unpredictable stress protocol. In both models of oxidative stress, gene and protein expression of Na+/K+-ATPase alpha 1 and alpha 3 isoforms within the higher and lower brain was remarkably stable. Thus, Na+/K+-ATPase function previously reported as altered by oxidative stress is not through induced changes in the expression of pump isoforms. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
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