自噬
穿心莲内酯
海马体
PI3K/AKT/mTOR通路
认知功能衰退
突触可塑性
化学
海马结构
内分泌学
内科学
药理学
医学
神经科学
生物
信号转导
细胞凋亡
生物化学
痴呆
受体
疾病
作者
Haiyu Zhang,Xinmei Xie,Jun-Zhuo Shi,Qian Zhao,Luo Dong-mei,Jiaojiao Hao,Yunfeng Zhou,Guang Han,Xiaobin Pang
摘要
Abstract The present study aims to investigate the cognition‐enhancing effect of 3, 14, 19‐Triacetyl andrographolide (ADA) on learning and memory deficits in 3 × Tg‐AD mice and to explore its underlying mechanism. Eight‐month‐old 3 × Tg‐AD mice and C57BL/6J mice were randomly divided into three groups, namely wild‐type group, 3 × Tg‐AD group, and 3 × Tg‐AD+ADA group (5 mg/kg, for 21 days, i.p.). We found that ADA significantly improved learning and cognition impairment, inhibited the loss of Nissl body, and reduced Aβ load in the brains of 3 × Tg‐AD mice. In addition, ADA enhanced the levels of PSD95 and SYP, which were closely associated with synaptic plasticity. Accumulated autophagosomes, LC3II, and P62 in hippocampus and cortex of 3 × Tg‐AD mice were decreased by ADA treatment. Furthermore, ADA administration further down‐regulated the expressions of p‐AKT and p‐mTOR, reduced the level of CTSB, and increased the co‐localization of LC3 and LAMP1 in the brains of 3 × Tg‐AD mice, implying that ADA‐induced autophagy initiation and also promoted the degradation process. In Aβ 25–35 ‐induced HT22 cells, ADA displayed similar effects on autophagy flux as observed in 3 × Tg‐AD mice. Our finding verified that ADA could improve synaptic plasticity and cognitive function, which is mainly attributed to the key roles of ADA in autophagy induction and degradation.
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