Department of Pharmacy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; The Key Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Chongqing Medical University, Chongqing, China.
Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; Laboratory Research Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Brain Res. 2021 Jan 15;1751:147197. doi: 10.1016/j.brainres.2020.147197. Epub 2020 Nov 5.
To investigate whether curcumin promotes hippocampal neurogenesis in the cerebral ischemia (CI) mice via Wnt/β-catenin signaling pathway.
Male C57BL/6 mice were randomly divided into groups: sham operation group (Sham), cerebral ischemic group (CI), curcumin treatment group (50, 100 mg/kg/d, i.p.) and curcumin (100 mg/kg/d) + DKK1 (a blocker of Wnt receptor, 200 ng/d, icv) group. CI was induced by bilateral common carotid arteries occlusion (BCCAO) for 20 min. The Morris water maze test was conducted to detect spatial learning and memory. Immunofluorescence staining was used to examine the proliferation and differentiation of immature neurons in the hippocampal dentate gyrus. The proteins involved in neurogenesis and Wnt signaling pathway were examined using Western blot assay.
Curcumin significantly alleviated cognitive deficits induced by CI. Curcumin dose-dependently increased the proliferation of neural stem cells and promoted the differentiation and maturation of newly generated neural cells into neurons. Curcumin also increased the expression of proteins involved in neurogenesis (including Ngn2, Pax6 and NeuroD 1) and the Wnt/β-catenin signaling pathway. Moreover, the forenamed effects of curcumin were abolished by pretreatment with DKK1, a blocker of Wnt receptor.
Curcumin promotes hippocampal neurogenesis by activating Wnt/β-catenin signaling pathway to ameliorate cognitive deficits after acute CI.
研究姜黄素是否通过 Wnt/β-连环蛋白信号通路促进脑缺血（CI）小鼠海马神经发生。
雄性 C57BL/6 小鼠随机分为以下几组：假手术组（Sham）、脑缺血组（CI）、姜黄素治疗组（50、100mg/kg/d，腹腔注射）和姜黄素（100mg/kg/d）+DKK1（Wnt 受体阻断剂，200ng/d，侧脑室注射）组。通过双侧颈总动脉闭塞（BCCAO）20min 诱导 CI。采用 Morris 水迷宫试验检测空间学习和记忆能力。免疫荧光染色检测海马齿状回未成熟神经元的增殖和分化。Western blot 检测神经发生和 Wnt 信号通路相关蛋白。
姜黄素显著减轻 CI 引起的认知功能障碍。姜黄素呈剂量依赖性增加神经干细胞的增殖，并促进新生成的神经细胞向神经元分化和成熟。姜黄素还增加了神经发生相关蛋白（包括 Ngn2、Pax6 和 NeuroD1）和 Wnt/β-连环蛋白信号通路的表达。此外，Wnt 受体阻断剂 DKK1 预处理可消除姜黄素的上述作用。
姜黄素通过激活 Wnt/β-连环蛋白信号通路促进海马神经发生，改善急性 CI 后认知功能障碍。
