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

Abstract

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 β-amyloid1-42 (Aβ1-42), 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.

Exogenous fibroblast growth factor 1 ameliorates diabetes-induced cognitive decline via coordinately regulating PI3K/AKT signaling and PERK signaling

“…Furthermore, Aβ 1-42 was largely deposited in the hippocampus of db/db mice, and synaptic dysfunction in the hippocampus was presented in db/db mice. These findings are consistent with our and others' previous studies [1,31]. With the increasing epidemic of FGF1 has dual function of normalizing hyperglycemia [23] and neuroprotection [32].…”

RNA‐binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration

“…Studies have demonstrated that autophagy plays a protective role in diabetes and IVDD 39 ; also, autophagy has been shown to combat against senescence 25 . Based on in vitro investigation, we found that HuR regulates senescence through autophagy.…”

Potential Biochemical Mechanisms of Brain Injury in Diabetes Mellitus

“…Increasing evidence indicated that DM is related to cognitive impairment, and the level of hyperglycemia and duration of DM have been shown to be linked with cognitive decline [23]. Cerebrovascular dysfunction is associated with cognitive impairment in patients with vascular dementia [24].…”