莫里斯水上航行任务
氧化应激
神经保护
突触素
药理学
蛋白激酶B
海马体
医学
认知功能衰退
突触蛋白I
内分泌学
内科学
PI3K/AKT/mTOR通路
奶油
细胞凋亡
化学
痴呆
生物化学
转录因子
免疫组织化学
基因
小泡
突触小泡
疾病
膜
作者
Beini Wang,Chengbiao Wu,Zimiao Chen,Pan Zheng,Yaqian Liu,Jie Xiong,Jingyu Xu,Peifeng Li,Abdullah Al Mamun,Libing Ye,Zhilong Zheng,Yanqing Wu,Jian Xiao,Jian Wang
标识
DOI:10.1038/s41401-020-00583-3
摘要
DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.
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