Research Paper Volume 15, Issue 16 pp 8298—8314
Gastrodin ameliorates cognitive dysfunction in diabetes by inhibiting PAK2 phosphorylation
- 1 Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China
- 2 Department of Pathology and Pathophysiology, Baoshan College of Traditional Chinese Medicine, Baoshan, China
- 3 College of Clinical Oncology, Kunming Medical University, Kunming, China
- 4 Academy of Biomedical Engineering, Kunming Medical University, Kunming, China
- 5 Institute of Drug Discovery and Development, Kunming Pharmaceutical Corporation, Kunming, China
- 6 Department of Morphological Laboratory, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China
- 7 The Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
- 8 The First Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
- 9 School of Nursing, Kunming Medical University, Kunming, China
- 10 Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Kunming Medical University, Kunming, China
Received: February 17, 2023 Accepted: July 14, 2023 Published: August 22, 2023
https://doi.org/10.18632/aging.204970How to Cite
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.