4.7 Article

Autophagy Activation is Associated with Neuroprotection in Diabetes-associated Cognitive Decline

Journal

AGING AND DISEASE
Volume 10, Issue 6, Pages 1233-1245

Publisher

INT SOC AGING & DISEASE
DOI: 10.14336/AD.2018.1024

Keywords

Diabetes-associated cognitive decline (DACD); Autophagy; Hippocampus; beta-amyloid; Apoptosis

Funding

  1. Zhejiang Provincial Natural Science Foundation [LQ18H090011, LY17H090017, LQ18H150003]
  2. National Natural Science Foundation of China [81472165, 81722028, 81801233, 81801245]

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Autophagy is a lysosome-dependent cellular catabolic mechanism that mediates the turnover of dysfunctional organelles and aggregated proteins. It has a neuroprotective role on neurodegenerative diseases. Here, we hypothesized that autophagy may also have a neuroprotective role in diabetes-associated cognitive decline (DACD). In current study, we found that db/db mice display cognitive decline with inferior learning and memory function. The accumulation of beta-amyloid(1-42) (A beta(1-42)), which is a characteristic of Alzheimer's disease (AD), was markedly higher in the prefrontal cortex (PFC), cornu ammon1 (CA1), and dentate gyrus (DG) areas of the hippocampus in db/db mice. Moreover, BDNF and microtubule associated protein 2 (MAP2) levels were lower in the hippocampus of db/db mice. However, there was no noticeable differences in the level of apoptosis in the hippocampus between control (CON) mice and db/db mice. Markers of autophagy in the hippocampus were elevated in db/db mice. The expression levels of ATG5, ATG7, and LC3B were higher, and the level of P62 was lower. An autophagy inhibitor, 3-MA, and ATG7 siRNA significantly reversed the activation of autophagy in vitro, which was accompanied with a higher level of apoptosis. Taken together, our current study suggests that diabetes is associated with cognitive decline, and activation of autophagy has a neuroprotective role in DACD.

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