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Research Paper|Volume 15, Issue 16|pp 8298—8314

Gastrodin ameliorates cognitive dysfunction in diabetes by inhibiting PAK2 phosphorylation

Zhi-Hao Mu1, Zhi-Min Zhao1,2, Su-Su Yang1,3, Lei Zhou4, Yi-Dan Liu5, Zhong-Yi Qian6, Xin-Jie Liu1,7, Peng-Chao Zhao1,8, Ren-Bo Tang1,7, Jia-Yin Li1,7, Jing-Yao Zeng8, Zhi-Hong Yang1, Yong-Hua Ruan1, Ying Zhang9, Yue-Qin Zeng4, Ying-Ying Zou1,10
  • 1Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China
  • 2Department of Pathology and Pathophysiology, Baoshan College of Traditional Chinese Medicine, Baoshan, China
  • 3College of Clinical Oncology, Kunming Medical University, Kunming, China
  • 4Academy of Biomedical Engineering, Kunming Medical University, Kunming, China
  • 5Institute of Drug Discovery and Development, Kunming Pharmaceutical Corporation, Kunming, China
  • 6Department of Morphological Laboratory, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China
  • 7The Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
  • 8The First Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
  • 9School of Nursing, Kunming Medical University, Kunming, China
  • 10Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Kunming Medical University, Kunming, China
* Equal contribution
Received: February 17, 2023Accepted: July 14, 2023Published: August 22, 2023

Copyright: © 2023 Mu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Diabetes is associated with higher prevalence of cognitive dysfunction, while the underlying mechanism is still elusive. In this study, we aim to explore the potential mechanism of diabetes-induced cognitive dysfunction and assess the therapeutic effects of Gastrodin on cognitive dysfunction. Diabetes was induced by a single injection of streptozotocin. The Morris Water Maze Test was employed to assess the functions of spatial learning and memory. Transcriptome was used to identify the potential factors involved. Western blot and immunofluorescence were applied to detect the protein expression. Our results have shown that spatial learning was impaired in diabetic rats, coupled with damaged hippocampal pyramidal neurons. Gastrodin intervention ameliorated the spatial learning impairments and neuronal damages. Transcriptomics analysis identified differential expression genes critical for diabetes-induced hippocampal damage and Gastrodin treatment, which were further confirmed by qPCR and western blot. Moreover, p21 activated kinase 2 (PAK2) was found to be important for diabetes-induced hippocampal injury and its inhibitor could promote the survival of primary hippocampal neurons. It suggested that PAK2 pathway may be involved in cognitive dysfunction in diabetes and could be a therapeutic target for Gastrodin intervention.