Sleeve gastrectomy attenuated diabetes-related cognitive decline in diabetic rats

Huanxin Ding; Chuxuan Liu; Shuo Zhang; Bingjun Li; Qian Xu; Bowen Shi; Songhan Li; Shuohui Dong; Xiaomin Ma; Yun Zhang; Mingwei Zhong; Guangyong Zhang

doi:10.3389/fendo.2022.1015819

Sleeve gastrectomy attenuated diabetes-related cognitive decline in diabetic rats

Front Endocrinol (Lausanne). 2022 Nov 3:13:1015819. doi: 10.3389/fendo.2022.1015819. eCollection 2022.

Authors

Huanxin Ding¹, Chuxuan Liu¹, Shuo Zhang², Bingjun Li³, Qian Xu³, Bowen Shi¹, Songhan Li⁴, Shuohui Dong¹, Xiaomin Ma³, Yun Zhang³, Mingwei Zhong³, Guangyong Zhang¹

Affiliations

¹ Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Medical Research Center, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
³ Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
⁴ Department of Breast Disease, Peking University People's Hospital, Beijing, China.

Abstract

Objective: To investigate the effects of sleeve gastrectomy (SG) on diabetes-related cognitive decline (DCD) in rats with diabetic mellitus (DM).

Methods and methods: Forty Wistar rats were randomly divided into control (CON) group (n=10), diabetes mellitus (DM) group (n=10), sham operation (SHAM) group (n=10) and SG group (n=10). DM model was established by high-fat diet (HFD) combined with intraperitoneal injection of streptozocin (STZ). Behavioral evaluation was given using Morris water maze test and Y-maze. In addition, PET-CT, TUNEL assay, histological analysis, transmission electron microscopy (TEM), immunohistochemistry (IHC) and Western blot analysis were used to evaluate the alleviating effects and potential mechanisms of SG on DCD in DM rats.

Results: Compared with the sham group, SG induced significant improvement in the metabolic indices such as blood glucose and body weight. Besides, it could attenuate the insulin resistance compared with SHAM group. In addition, SG could improve the cognitive function of DM rats, which were featured by significant decrease in the escape latency (P<0.05), and significant increase in the time in target quadrant and platform crossings (P<0.05) compared with the SHAM group. SG induced significant elevation in the spontaneous alternation compared with SHAM group (P<0.05). Moreover, SG could improve the arrangement and biosynthesis of hippocampus neuron. Moreover, SG triggered the inhibition of apoptosis of hippocampus neurons, and Western blot analysis showed SG induced significant increase in the ratios of Bcl-2/Bax and Caspase3/cleaved Caspase 3. TEM demonstrated SG could significantly improve the microstructure of hippocampus neurons compared with the SHAM group. Western blot and IHC confirmed the significant decrease in the phosphorylation of tau at Ser404 and Ser396 sites in the SG group. Furthermore, SG activated the PI3K signaling pathway by elevating the phosphorylation of PI3K and Akt and GSK3β compared with the SHAM group.

Conclusion: SG attenuated the DCD in DM rats, which may be related to the activation of PI3K signaling pathway.

Keywords: PI3K; diabetes-related cognitive decline; neuronal apoptosis; sleeve gastrectomy; tau.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cognitive Dysfunction* / etiology
Cognitive Dysfunction* / prevention & control
Diabetes Mellitus, Experimental* / metabolism
Gastrectomy / methods
Phosphatidylinositol 3-Kinases
Positron Emission Tomography Computed Tomography
Rats
Rats, Wistar

Substances

Phosphatidylinositol 3-Kinases