Affiliations: Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
Correspondence:
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Correspondence to: Yuan Zhong, Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yi Shan Road, Shanghai 200233, China. Tel.: +86 2124056227; E-mail: zhongyuan_zhy@163.com.
Note: [1] These authors contributed equally to this work.
Abstract: Recent studies suggest that diabetes predisposes patients to develop neurodegenerative Alzheimer’s disease (AD), although the underlying mechanisms have yet to be determined. Compromised autophagy of neuronal cells, which occurs in the early stages of AD, has been shown to enhance disease progression. However, autophagic regulation as a mechanism connecting diabetes and AD has not been shown before. Here, we found that streptozotocin (STZ)-induced diabetic rats exhibited poorer performance on the social recognition test, Morris water maze, and plus-maze discriminative avoidance task, compared to PBS-treated normoglycemic control rats, likely resulting from increased brain deposition of amyloid-β peptide aggregates (Aβ) and increased phosphorylation of tau protein, two pathological features of AD. Moreover, diabetes-induced AD-like behavioral and pathological changes were associated with a decrease in neuronal cell autophagy. Furthermore, compromised cell autophagy was recapitulated in vitro in neuronal cells cultured in high glucose conditions. Thus, our data suggest that hyperglycemia in diabetes may directly inhibit neuronal cell autophagy, which subsequently enhances AD-associated pathological progression.
Keywords: Alzheimer’s disease, amyloid-β peptide aggregates, autophagy, diabetes, tau
