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Abstract
Gastrodin (GAS), an active constituent extracted from Gastrodia elata Blume, is used to treat ischemic stroke, epilepsy, dizziness, and dementia for centuries in China. This study examined its effects on vascular dementia (VD) and the underlying molecular mechanisms. VD was established by ligation of bilateral common carotid artery occlusion (BCCAO). A total of 7 days after BCCAO surgery, GAS (15, 30, and 60 mg/kg) was orally administered for 28 consecutive days to evaluate therapeutic effects. Cognitive function was tested by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin–Eosin staining. Flow cytometry was used for evaluating apoptosis in the hippocampi. The target protein expression was examined by Western blot. The results showed that BCCAO induced cognitive impairment, hippocampus CA1 and CA3 pyramidal neuron damage, beta-amyloid (Aβ) deposition, excessive autophagy, and apoptosis. GAS treatment significantly improved BCCAO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that GAS exerted the protective effect via reducing the levels of Aβ1–40/42, APP, and β-site APP-cleaving enzyme 1 expression, and increasing Aβ-related protein, a disintegrin and metalloprotease 10, and insulin degrading enzyme expression. Meanwhile, GAS inhibited excessive autophagy via decreasing Beclin-1, LC3-II, and p62 levels. Furthermore, GAS inhibited apoptosis through the downregulation of Bax and upregulation of Bcl-2. Moreover, P38 MAPK signaling pathway was involved in the process. Our findings demonstrate that GAS was effective in the treatment of BCCAO-induced VD via targeting Aβ-related protein formation and inhibiting autophagy and apoptosis of hippocampus neurons.
Highlights
Vascular dementia (VD), a kind of acquired intelligence damaging syndrome, is characterized by neurodegeneration, cognitive impairment, and memory difficulty
Bilateral common carotid artery occlusion (BCCAO) in rats is widely accepted as an experimental model, which can imitate the pathological change occurred in VD successfully (Jiwa et al, 2010)
Results showed that rats in bilateral common carotid artery occlusion (BCCAO) group presented worse memory ability with spent less time in the platform quadrant than that of Sham and Sham + GAS (60 mg/kg) groups (P < 0.05)
Summary
Vascular dementia (VD), a kind of acquired intelligence damaging syndrome, is characterized by neurodegeneration, cognitive impairment, and memory difficulty. With an urgent demand for novel neuroprotective strategies to treatment of VD, numerous studies have been taken to search effective therapies Among these studies, bilateral common carotid artery occlusion (BCCAO) in rats is widely accepted as an experimental model, which can imitate the pathological change occurred in VD successfully (Jiwa et al, 2010). Aβ mediated autophagy flux and accumulation of autophagosomes, and the inhibition of autophagy decreased Aβ-induced cytotoxicity after BCCAO injury (Nagatani et al, 2012; Zou et al, 2017) Other mechanisms such as apoptosis of hippocampal neurons may be triggered by the accumulation of Aβ (Zhang Y. et al, 2016; Xiong et al, 2017)
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