Melatonin reduces hippocampal beta-amyloid generation in rats exposed to chronic intermittent hypoxia

Brain Research
Kwong-Man NgMan-Lung Fung

Abstract

The deposition of neurotoxic beta-amyloid plaques plays a central role in the pathogenesis of Alzheimer's disease. At the molecular level, the generation of beta-amyloid peptides involves the site-specific cleavage of the precursor protein by beta-site APP cleavage enzyme (BACE) and presenilin. Although acute or chronic sustained hypoxia appears to increase the generation of beta-amyloid peptides via the HIF-1 alpha dependent upregulation of BACE, the effect of chronic intermittent hypoxia (CIH) on the generation of beta-amyloid peptides remains uncertain. In this study, we have evaluated such contention in the rat hippocampus, and we found that short-term CIH exposure (3 days) caused significant increases in the generation of beta-amyloid peptides, and the expressions of BACE, presenilin and HIF-1 alpha protein levels, in the hippocampus of CIH rats. Moreover, the CIH-induced hippocampal beta-amyloid peptide generation could be abolished by a daily pharmacological administration of melatonin (10mg/kg), which reduced the BACE but not presenilin expression. Also, there were no significant differences in the hippocampal HIF-1 alpha protein levels between the melatonin- and vehicle-treated CIH groups. Our study not only provided t...Continue Reading

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Citations

Feb 5, 2011·Journal of Neuropathology and Experimental Neurology·Charanjit KaurEng-Ang Ling
Jan 5, 2011·International Journal of Alzheimer's Disease·Venkatramanujam SrinivasanDaniel P Cardinali
May 21, 2013·American Journal of Alzheimer's Disease and Other Dementias·Alka KaushalKiran Dip Gill
Jan 25, 2017·The International Journal of Neuroscience·Yating PengRuoyun Ouyang
Mar 13, 2017·Journal of the Mechanical Behavior of Biomedical Materials·Ignasi JorbaIsaac Almendros
Feb 8, 2019·Neurotoxicity Research·Alka KaushalJyotdeep Kaur
May 22, 2018·Journal of Alzheimer's Disease : JAD·Andreia G AndradeRicardo S Osorio
Jan 4, 2021·Sleep & Breathing = Schlaf & Atmung·Seung Min InHyun Jun Kim
Feb 23, 2021·Journal of Alzheimer's Disease : JAD·Yang-Yang WangZhi-You Cai
Dec 2, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yuanming LiJinhao Sun
Apr 17, 2021·Ageing Research Reviews·Johannes BurtscherGrégoire P Millet

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