Exenatide exerts a neuroprotective effect against diabetic cognitive impairment in rats by inhibiting apoptosis: Role of the JNK/c‑JUN signaling pathway

Wang,Gengyin; Zhao,Zongquan; Ren,Bo; Yu,Wu; Zhang,Xudong; Liu,Jiang; Wang,Liping; Si,Daowen; Yang,Meiliu

doi:10.3892/mmr.2022.12627

Exenatide exerts a neuroprotective effect against diabetic cognitive impairment in rats by inhibiting apoptosis: Role of the JNK/c‑JUN signaling pathway

Authors:
- Gengyin Wang
- Zongquan Zhao
- Bo Ren
- Wu Yu
- Xudong Zhang
- Jiang Liu
- Liping Wang
- Daowen Si
- Meiliu Yang
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Affiliations: Department of Human Anatomy, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China, General Practice, Pingjiang Xincheng Community Health Service Center, Suzhou, Jiangsu 215101, P.R. China, Medical Experimental Center, Jitang College of North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China, School Hospital, Hengshui University, Hengshui, Hebei 053010, P.R. China, Department of Life Sciences, Hengshui University, Hengshui, Hebei 053010, P.R. China
Published online on: February 2, 2022 https://doi.org/10.3892/mmr.2022.12627
Article Number: 111
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Exenatide could reduce blood glucose and alleviate cognitive dysfunction induced by diabetes mellitus (DM). In the present study, a diabetic model was established in Sprague‑Dawley rats to further explore the mechanism of exenatide on diabetes‑induced cognitive impairment. Notably, the model rats performed poorly in the Morris water maze test and had more apoptotic neurons compared with the control rats. By contrast, exenatide attenuated cognitive impairment and inhibited neuronal apoptosis in the DM rat model. To explore the neuroprotective mechanisms of exenatide, western blotting was performed to detect the expression levels of markers of endoplasmic reticulum stress, including cytochrome c (Cyt‑c), Caspase‑3, JNK and c‑JUN, in hippocampal tissue. Reverse transcription‑quantitative PCR was also performed to measure the mRNA expression levels of Cyt‑c and Caspase‑3. After 16 weeks of treatment, exenatide treatment downregulated Cyt‑c, Caspase‑3, phosphorylated (p)‑JNK and p‑c‑JUN expression in the hippocampal tissue of diabetic rats. Moreover, Cyt‑c, Caspase‑3, JNK and JUN expression levels were detected following treatment with a specific inhibitor of JNK (SP600125). The results revealed that SP600125 had similar inhibitory effects on the JNK pathway and ERS‑related protein expression (Cyt‑t, Caspase‑3, p‑JNK and p‑c‑JUN). These results suggested that exenatide improved cognitive dysfunction in DM rats and that the underlying mechanism may be associated with inhibiting apoptosis by suppressing the activation of JNK/c‑JUN.

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