Gastrodin relieves cognitive impairment by regulating autophagy via PI3K/AKT signaling pathway in vascular dementia

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated P62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/AKT pathway-related proteins expression, which regulates autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive autophagy and apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/AKT pathway-mediated autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.

Related collections

Most cited references 35

Record: found
Abstract: found
Article: not found

The prevalence of dementia in urban and rural areas of China.

Jianping Jia, Fen Wang, Cuibai Wei … (2014)

The Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas. For the years 2008 to 2009, we performed a population-based cross-sectional survey with a multistage cluster sampling design. Residents aged 65 years and older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities across China. Participants were assessed with a series of clinical examinations and neuropsychological measures. Dementia, AD, and VaD were diagnosed according to established criteria via standard diagnostic procedures. The prevalence of dementia, AD, and VaD among individuals aged 65 years and older were 5.14% (95% CI, 4.71-5.57), 3.21% (95% CI, 2.87-3.55), and 1.50% (95% CI, 1.26-1.74), respectively. The prevalence of dementia was significantly higher in rural areas than in urban ones (6.05% vs. 4.40%, P < .001). The same regional difference was also seen for AD (4.25% vs. 2.44%, P < .001) but not for VaD (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample was stratified by educational level. Moreover, the risk factors for AD and VaD differed for urban and rural populations. A notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban-rural differences. Copyright © 2014. Published by Elsevier Inc.

0 comments Cited 202 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: found

Is Open Access

A Review on Central Nervous System Effects of Gastrodin

Yuan Liu, Jialiang Gao, Min Peng … (2018)

Rhizoma Gastrodiae (also known as Tian ma), the dried rhizome of Gastrodia elata Blume, is a famous Chinese herb that has been traditionally used for the treatment of headache, dizziness, spasm, epilepsy, stoke, amnesia and other disorders for centuries. Gastrodin, a phenolic glycoside, is the main bioactive constituent of Rhizoma Gastrodiae. Since identified in 1978, gastrodin has been extensively investigated on its pharmacological properties. In this article, we reviewed the central nervous system (CNS) effects of gastrodin in preclinical models of CNS disorders including epilepsy, Alzheimer's disease, Parkinson's disease, affective disorders, cerebral ischemia/reperfusion, cognitive impairment as well as the underlying mechanisms involved and, where possible, clinical data that support the pharmacological activities. The sources and pharmacokinetics of gastrodin were also reviewed here. As a result, gastrodin possesses a broad range of beneficial effects on the above-mentioned CNS diseases, and the mechanisms of actions include modulating neurotransmitters, antioxidative, anti-inflammatory, suppressing microglial activation, regulating mitochondrial cascades, up-regulating neurotrophins, etc. However, more detailed clinical trials are still in need for positioning it in the treatment of neurological disorders.