Effect of the ZiBuPiYin Recipe on Diabetes-Associated Cognitive Decline in Zucker Diabetic Fatty Rats After Chronic Psychological Stress.

Tingting Bi,Wen Zhou,Libin Zhan,Hua Sui

doi:10.3389/fpsyt.2020.00272

Abstract

BackgroundCognitive impairment is a complication of type 2 diabetes mellitus (T2DM) that affects the central nervous system (CNS). Studies have shown that chronic psychological stress may promote the development of T2DM into diabetes-associated cognitive decline (DACD). Previously, cognitive impairment in T2DM was correlated predominantly with insulin resistance in the medial prefrontal cortex (mPFC).AimsWe examined the effect of the ZiBuPiYin recipe (ZBPYR) on Zucker diabetic fatty (ZDF) rats and explored the impact of chronic stress on altered β-amyloid (Aβ) metabolism through insulin receptor substrate (IRS) 1/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway after the induction of chronic psychological stress.Main MethodsAfter chronic psychological stress and drug treatment, cognitive function was observed via behavioral experiments. The activation of the hypothalamus-pituitary-adrenal (HPA) axis and levels of Aβ were detected by enzyme-linked immunosorbent assay, and the expression of related proteins was evaluated by Western blotting.Key FindingsZBPYR treatment significantly decreased anxious-like behaviors and plasma corticosterone (CORT) levels, and ameliorated learning and memory impairments of ZDF rats after chronic psychological stress. ZBPYR also reduced the deposition of Aβ in the mPFC, improved brain insulin resistance, and modulated the mTOR-autophagy pathway.SignificanceZBPYR may be a potential therapeutic application for the treatment of DACD induced by chronic psychological stress.

Highlights

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, increased insulin resistance over time, and progressive failure of pancreatic insulin secretion [1]
We examined the effect of the ZiBuPiYin recipe (ZBPYR) on Zucker diabetic fatty (ZDF) rats and explored the impact of chronic stress on altered b-amyloid (Ab) metabolism through insulin receptor substrate (IRS) 1/protein kinase B (AKT)/mammalian target of rapamycin signaling pathway after the induction of chronic psychological stress
Performance in the visible platform version was similar across groups in terms of escape latency (Figure 5D). All these findings suggest that ZBPYR could attenuate the impairment of learning and memory impairments caused by chronic psychological stress in ZDF rats

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, increased insulin resistance over time, and progressive failure of pancreatic insulin secretion [1]. Epidemiologic studies have reported that the worldwide prevalence of diabetes mellitus is expected to increase from 425 million in 2017 to an estimated 629 million in 2045 [2]. Both cross-sectional and longitudinal studies reported that T2DM is associated with Alzheimer's disease (AD) [3], mild cognitive impairment (MCI) [4], anxiety, and depression [5]. Cognitive impairment in T2DM was correlated predominantly with insulin resistance in the medial prefrontal cortex (mPFC)

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