Dl‑3n‑butylphthalide improves spatial learning and memory in rats with vascular dementia by reducing autophagy via regulation of the mTOR signaling pathway

Tian,Ayong; Ma,Xiaochuan; Li,Hui; Zhang,Rongwei

doi:10.3892/etm.2019.8402

Dl‑3n‑butylphthalide improves spatial learning and memory in rats with vascular dementia by reducing autophagy via regulation of the mTOR signaling pathway

Authors:
- Ayong Tian
- Xiaochuan Ma
- Hui Li
- Rongwei Zhang
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Gerontology and Geriatrics, The Third Hospital of Shenyang, Shenyang, Liaoning 110001, P.R. China, Department of Gerontology and Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: December 31, 2019 https://doi.org/10.3892/etm.2019.8402
Pages: 1940-1946

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Abstract

Dl‑3n‑butylphthalide (NBP) has been reported to be a beneficial and promising drug for the treatment and prevention of vascular dementia (VD). NBP has been demonstrated to improve learning and memory in rats with vascular cognitive impairment by activating the silent information regulator 1/brain‑derived neurotrophic factor pathway. However, NBP is a multi‑target drug. Therefore, the present study aimed to determine whether the protective effects of NBP on learning deficits in a rat model of VD were due to the inhibition of autophagy via the phosphorylated mammalian target of rapamycin (p‑mTOR) pathway. NBP treatment attenuated memory damage in rats with VD, as demonstrated by T‑maze and Morris water maze tests. NBP administration also significantly reduced the levels of the characteristic autophagic proteins Beclin 1 and LC3II and upregulated phosphorylation levels of mTOR at Ser‑2448 compared with the VD group. However, treatment of rats with VD with NBP plus the mTOR inhibitor rapamycin failed to significantly suppress Beclin 1 and LC3II expression. These results suggested that the beneficial effects of NBP on learning deficits in a rat model of VD were due to the suppression of ischemia‑induced autophagy via the p‑mTOR signaling pathway.

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