Research Paper Volume 13, Issue 7 pp 9542—9565
Gastrodin ameliorates learning and memory impairment in rats with vascular dementia by promoting autophagy flux via inhibition of the Ca2+/CaMKII signal pathway
- 1 The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, P.R. China
- 2 Guiyang Maternal and Child Health-Care Hospital, Guiyang 550000, P.R. China
- 3 The Key Laboratory of Optimal Utilization of Natural Medicine Resources and The Union Key Laboratory of Guiyang City, Guizhou Medical University, School of Pharmaceutical Sciences, Guiyang 550025, P.R. China
- 4 The Key Laboratory of Endemic and Ethnic Diseases of Ministry of Education, Guizhou Medical University, Guiyang 550025, P.R. China
Received: March 7, 2020 Accepted: November 30, 2020 Published: March 10, 2021https://doi.org/10.18632/aging.202667
How to Cite
Copyright: © 2021 Chen 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.
Vascular dementia (VD) is a common disease that occurs during human aging. Gastrodin (GAS) has potential benefits for the prevention and treatment of VD. In the present study, we investigated the effects of GAS on cognitive dysfunction in rats with VD induced by permanent middle cerebral artery occlusion (pMCAO) and explored the underlying mechanism. Immunohistochemical and western blot analyses revealed that GAS attenuated hippocampal levels of LC3 (microtubule-associated protein 1 light chain 3), p62, and phosphorylated CaMKII (Ca2+-calmodulin stimulated protein kinase II) in VD rats. Additionally, our results revealed that cobalt chloride blocked autophagic flux in HT22 cells, which was confirmed by increased levels of LC3 and p62 when combined with chloroquine. Notably, GAS ameliorated the impaired autophagic flux. Furthermore, we confirmed that GAS combined with KN93 (a CaMKII inhibitor) or CaMKII knockdown did not impact the reduced p62 levels when compared with GAS treatment alone. Furthermore, a co-immunoprecipitation assay demonstrated that endogenous p62 bound to CaMKII, as confirmed by mass spectrometric analysis after the immunoprecipitation of p62 from HT22 cells. These findings revealed that GAS attenuated autophagic flux dysfunction by inhibiting the Ca2+/CaMKII signaling pathway to ameliorate cognitive impairment in VD.