Orexin-A exacerbates Alzheimer's disease by inducing mitochondrial impairment.
Neurosci Lett
; 718: 134741, 2020 01 23.
Article
in En
| MEDLINE
| ID: mdl-31927055
ABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disease which is characterized by the accumulation of amyloid-ß peptide (Aß). Orexin-A is a neuropeptide which has been reported to participate in the pathogenesis of AD. Thus, we aimed to investigate the possible mechanism by which Orexin-A acts in AD. APP/PS1 transgenic mice, an animal model of AD, were intracerebroventricularly injected with Orexin-A. Aß-treated SH-SY5Y cells were used as a cell model of AD and treated with Orexin-A. The Morris water maze test, fluorescence microscopy, enzyme-linked immunosorbent assay (ELISA), electron microscopy, real-time PCR, and other biochemical assays were conducted. The Morris water maze test showed that Orexin-A aggravated cognitive deficit in APP/PS1 mice. Using thioflavine-S staining and ELISA, we found that Orexin-A promoted Aß accumulation in APP/PS1 mice. By evaluating mitochondrial morphology, cytochrome c oxidase activity, ATP level, mitochondrial DNA copy number, and reactive oxygen species, we found that Orexin-A aggravated mitochondrial impairment in APP/PS1 mice and Aß-treated SH-SY5Y cells. Our results indicate that Orexin-A exacerbates AD by inducing mitochondrial impairment. This is a new mechanism that explains how Orexin-A participates in the pathogenesis of AD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alzheimer Disease
/
Orexins
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Morris Water Maze Test
/
Mitochondria
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Neurosci Lett
Year:
2020
Type:
Article
Affiliation country:
China