3‑N‑Butyphthalide improves learning and memory in rats with vascular cognitive impairment by activating the SIRT1/BDNF pathway

Tian,Ayong; Li,Wan; Zai,Qing; Li,Hui; Zhang,Rong‑Wei

doi:10.3892/mmr.2020.11106

3‑N‑Butyphthalide improves learning and memory in rats with vascular cognitive impairment by activating the SIRT1/BDNF pathway

Authors:
- Ayong Tian
- Wan Li
- Qing Zai
- Hui Li
- Rong‑Wei 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 Neurology, The Ninth People's Hospital of Shenyang, Shenyang, Liaoning 110024, 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: May 4, 2020 https://doi.org/10.3892/mmr.2020.11106
Pages: 525-533
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vascular cognitive impairment (VCI) is a type of cerebral vascular disorder that leads to learning and memory decline. VCI models can be induced by chronic cerebral hypoperfusion via permanent bilateral common carotid artery occlusion. 3‑N‑Butylphthalide (NBP) is a neuroprotective drug used for the treatment of ischemic cerebrovascular diseases. Silent information regulator 1 (SIRT1) plays an important role in memory formation and cognitive performance, and its abnormal reduction is associated with cognitive dysfunction in neurodegenerative diseases. Brain‑derived neurotrophic factor (BDNF) is a neurotrophic factor that plays critical roles in promoting neuronal growth and injury repair. The present study was performed to investigate the effects and the underlying mechanism of NBP on learning deficits in a rat model of VCI. Rats were divided into a control group, model group, low‑NBP‑dose group (30 mg/kg/day), high‑NBP‑dose group (60 mg/kg/day), NBP + SIRT1 inhibitor group and NBP + BDNF inhibitor group. Rats were then subjected to Morris water maze and T‑maze tests, which identified that NBP treatment significantly attenuated memory impairments in VCI rats. Molecular examination indicated that SIRT1 and BDNF expression levels in the hippocampus were increased by NBP treatment. However, NBP failed to ameliorate cognitive function after inhibition of the SIRT1/BDNF signaling pathway. In addition, NBP in combination with a SIRT1 inhibitor suppressed BDNF protein expression, but inhibition of BDNF did not inhibit SIRT1 protein expression in rats with VCI. The present results suggested that the neuroprotective effects of NBP on learning deficits in a rat model of VCI may be via regulation of the SIRT1/BDNF signaling pathway, in which SIRT1 may be the upstream signaling molecule. Therefore, the SIRT1/BDNF pathway could be a potential therapeutic target for VCI.

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