Open AccessGastrodin ameliorates learning and memory impairment in rats with vascular dementia by promoting autophagy flux via inhibition of the Ca2+/CaMKII signal pathway
Author(s) -
Tingting Chen,
Xiao Zhou,
Yini Xu,
Yue Li,
Xiaoshuai Wu,
Quan Xiang,
Lingyun Fu,
Xiaoxia Hu,
Ling Tao,
Xiangchun Shen
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202667
Subject(s) - gastrodin , autophagy , vascular dementia , flux (metallurgy) , signal pathway , memory impairment , dementia , neuroscience , signal (programming language) , signal transduction , medicine , chemistry , pharmacology , microbiology and biotechnology , biology , biochemistry , computer science , cognition , organic chemistry , programming language , apoptosis , disease , chromatography
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 (Ca 2+ -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 Ca 2+ /CaMKII signaling pathway to ameliorate cognitive impairment in VD.