Beta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer's disease mice.
Beta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer's disease mice.
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β2-肾上腺素能受体激活可增强阿尔茨海默病小鼠的神经发生。
DOI：
10.4103/1673-5374.193241
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发表时间：
2016-10
影响因子：
6.1
通讯作者：
Zhao P
中科院分区：
文献类型：
--
作者：
Chai GS;Wang YY;Yasheng A;Zhao P
海马神经发生受损是阿尔茨海默病的早期病理特征之一。增强成年海马神经发生已被视为阿尔茨海默病的潜在治疗策略。最近的研究表明，环境新奇性激活β2-肾上腺素能信号，并防止淀粉样β寡聚体引起的记忆障碍。在此，我们假设β2-肾上腺素能受体激活会增强神经发生并改善阿尔茨海默病的记忆缺陷。为了验证这一假设，我们研究了β2-肾上腺素受体激活对淀粉样前体蛋白/早老素1（APP/PS1）小鼠神经发生和记忆的作用和机制，使用激动剂克伦特罗（腹腔注射，2 mg/kg）。我们发现，β2-肾上腺素受体激活增强海马神经发生，改善记忆缺陷，增加树突分支和树突棘密度。这些作用与APP/PS1小鼠突触后密度95、突触蛋白1和突触素的上调有关。此外，β2-肾上腺素能受体激活通过减少Thr 668处的APP磷酸化来减少脑淀粉样斑块。这些结果表明，β2-肾上腺素能受体激活增强神经发生和改善APP/PS1小鼠的记忆缺陷。
Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer's disease. Enhancing adult hippocampal neurogenesis has been pursued as a potential therapeutic strategy for Alzheimer's disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer's disease. To test this hypothesis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 (APP/PS1) mice using the agonist clenbuterol (intraperitoneal injection, 2 mg/kg). We found that β2-adrenoceptor activation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines. These effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS1 mice.