All‐trans retinoic acid improved impaired proliferation of neural stem cells and suppressed microglial activation in the hippocampus in an Alzheimer's mouse model
All‐trans retinoic acid improved impaired proliferation of neural stem cells and suppressed microglial activation in the hippocampus in an Alzheimer's mouse model
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DOI：
10.1002/jnr.23843
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发表时间：
2017-03
影响因子：
4.2
通讯作者：
Risa Takamura;Naoto Watamura;Miyu Nikkuni;T. Ohshima
中科院分区：
文献类型：
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作者：
Risa Takamura;Naoto Watamura;Miyu Nikkuni;T. Ohshima
阿尔茨海默病(AD)是一种最常见的神经退行性疾病，以认知功能障碍和神经元丢失为特征。阿尔茨海默病患者的数量有所增加，但目前的治疗方法都不能阻止AD患者的进行性症状。据报道，小胶质细胞的激活会导致有害的慢性炎症，导致神经元死亡。此外，在淀粉样斑块形成之前，已经观察到成年海马区神经发生的损害。炎症反应可能导致阿尔茨海默病患者成年神经发生受损。本研究利用APPswe/PS1M146V/tauP301L(3×Tg)小鼠研究成年神经发生与神经炎症的关系。我们观察到3×Tg小鼠12个月龄时，神经干细胞的增殖能力下降，海马区出现严重炎症。此前，我们的研究表明全反式维甲酸(ATRA)在3×TG小鼠脑内具有抗炎作用。我们发现全反式维甲酸在抑制激活的小胶质细胞的同时，对海马区的增殖细胞的恢复也有影响。这些结果表明，全反式维甲酸抑制小胶质细胞的激活导致AD模型小鼠海马区成年神经发生的恢复。©2016 Wiley期刊，Inc.
Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive impairment with neuronal loss. The number of patients suffering from AD has increased, but none of the present therapies stops the progressive symptoms in patients with AD. It has been reported that the activation of microglial cells induces harmful chronic inflammation, leading to neuronal death. Furthermore, the impairment of adult neurogenesis in the hippocampus has been observed earlier than amyloid plaque formation. Inflammatory response may lead to impaired adult neurogenesis in patients with AD. This study examines the relationship between adult neurogenesis and neuroinflammation using APPswe/PS1M146V/tauP301L (3 × Tg) mice. We observed a decline in the proliferation of neural stem cells and the occurrence of severe inflammation in the hippocampus of 3 × Tg mouse brains at 12 months of age. Previously, our research had shown an anti‐inflammatory effect of all‐trans retinoic acid (ATRA) in the 3 × Tg mouse brain. We found that ATRA has effects on the recovery of proliferative cells along with suppression of activated microglia in the hippocampus. These results suggest that the inhibition of microglial activation by ATRA leads to recovery of adult neurogenesis in the hippocampus in an AD mouse model. © 2016 Wiley Periodicals, Inc.