长时程增强
海马体
粒体自噬
树突棘
突触可塑性
突触素
帕金
神经科学
认知功能衰退
内分泌学
内科学
品脱1
兴奋剂
突触后密度
海马结构
自噬
生物
医学
受体
痴呆
帕金森病
疾病
免疫组织化学
细胞凋亡
生物化学
作者
Hong-Yan Cai,Dan Yang,Jing Qiao,Junting Yang,Zhao-Jun Wang,Meina Wu,Jin‐Shun Qi,Christian Hölscher
摘要
Background: Alzheimer’s disease (AD) is a degenerative disorder, accompanied by progressive cognitive decline, for which there is no cure. Recently, the close correlation between AD and type 2 diabetes mellitus (T2DM) has been noted, and a promising anti-AD strategy is the use of anti-T2DM drugs. Objective: To investigate if the novel glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist DA4-JC shows protective effects in the triple APP/PS1/tau mouse model of AD. Methods: A battery of behavioral tests were followed by in vivo recording of long-term potentiation (LTP) in the hippocampus, quantified synapses using the Golgi method, and biochemical analysis of biomarkers. Results: DA4-JC improved cognitive impairment in a range of tests and relieved pathological features of APP/PS1/tau mice, enhanced LTP in the hippocampus, increased numbers of synapses and dendritic spines, upregulating levels of post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), normalized volume and numbers of mitochondria and improving the phosphatase and tensin homologue induced putative kinase 1 (PINK1) - Parkin mitophagy signaling pathway, while downregulating amyloid, p-tau, and autophagy marker P62 levels. Conclusion: DA4-JC is a promising drug for the treatment of AD.
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