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Abstract：
BACKGROUND: This work elucidated the effect of honokiol (HKL) on hippocampal neuronal mitochondrial function in Alzheimer\'s disease (AD).
METHODS: APP/PS1 mice were used as AD mice models and exposed to HKL and 3-TYP. Morris water maze experiment was performed to appraise cognitive performance of mice. Hippocampal Aβ+ plaque deposition and neuronal survival was evaluated by immunohistochemistry and Nissl staining. Hippocampal neurons were dissociated from C57BL/6 mouse embryos. Hippocampal neuronal AD model was constructed by Aβ oligomers induction and treated with HKL, CsA and 3-TYP. Neuronal viability and apoptosis were detected by cell counting kit-8 assay and TUNEL staining. mRFP-eGFP-LC3 assay, MitoSOX Red, dichlorodihydrofluorescein diacetate, and JC-1 staining were performed to monitor neuronal autophagosomes, mitochondrial reactive oxygen species (ROS), neuronal ROS, and mitochondrial membrane potential. Autophagy-related proteins were detected by Western blot.
RESULTS: In AD mice, HKL improved cognitive function, relieved hippocampal Aβ1-42 plaque deposition, promoted hippocampal neuron survival, and activated hippocampal SIRT3 expression and mitochondrial autophagy. These effects of HKL on AD mice were abolished by 3-TYP treatment. In hippocampal neuronal AD model, HKL increased neuronal activity, attenuated neuronal apoptosis and Aβ aggregation, activated SIRT3 and mitochondrial autophagy, reduced mitochondrial and neuronal ROS, and elevated mitochondrial membrane potential. CsA treatment and 3-TYP treatment abrogated the protection of HKL on hippocampal neuronal AD model. The promotion of mitochondrial autophagy by HKL in hippocampal neuronal AD model was counteracted by 3-TYP.
CONCLUSIONS: HKL activates SIRT3-mediated mitochondrial autophagy to mitigate hippocampal neuronal damage in AD. HKL may be effective in treating AD.
METHODS: APP/PS1 mice were used as AD mice models and exposed to HKL and 3-TYP. Morris water maze experiment was performed to appraise cognitive performance of mice. Hippocampal Aβ+ plaque deposition and neuronal survival was evaluated by immunohistochemistry and Nissl staining. Hippocampal neurons were dissociated from C57BL/6 mouse embryos. Hippocampal neuronal AD model was constructed by Aβ oligomers induction and treated with HKL, CsA and 3-TYP. Neuronal viability and apoptosis were detected by cell counting kit-8 assay and TUNEL staining. mRFP-eGFP-LC3 assay, MitoSOX Red, dichlorodihydrofluorescein diacetate, and JC-1 staining were performed to monitor neuronal autophagosomes, mitochondrial reactive oxygen species (ROS), neuronal ROS, and mitochondrial membrane potential. Autophagy-related proteins were detected by Western blot.
RESULTS: In AD mice, HKL improved cognitive function, relieved hippocampal Aβ1-42 plaque deposition, promoted hippocampal neuron survival, and activated hippocampal SIRT3 expression and mitochondrial autophagy. These effects of HKL on AD mice were abolished by 3-TYP treatment. In hippocampal neuronal AD model, HKL increased neuronal activity, attenuated neuronal apoptosis and Aβ aggregation, activated SIRT3 and mitochondrial autophagy, reduced mitochondrial and neuronal ROS, and elevated mitochondrial membrane potential. CsA treatment and 3-TYP treatment abrogated the protection of HKL on hippocampal neuronal AD model. The promotion of mitochondrial autophagy by HKL in hippocampal neuronal AD model was counteracted by 3-TYP.
CONCLUSIONS: HKL activates SIRT3-mediated mitochondrial autophagy to mitigate hippocampal neuronal damage in AD. HKL may be effective in treating AD.
摘要：
背景：这项工作阐明了和厚朴酚（HKL）对阿尔茨海默病（AD）中海马神经元线粒体功能的影响。
方法：APP/PS1小鼠作为AD小鼠模型，暴露于HKL和3-TYP。进行Morris水迷宫实验以评估小鼠的认知能力。通过免疫组织化学和Nissl染色评估海马Aβ斑块沉积和神经元存活。海马神经元与C57BL/6小鼠胚胎分离。通过Aβ寡聚体诱导构建海马神经元AD模型，并用HKL处理，CsA和3-TYP。通过细胞计数试剂盒-8测定和TUNEL染色检测神经元活力和凋亡。mRFP-eGFP-LC3测定，MitoSOX红,二氯二氢荧光素二乙酸酯，和JC-1染色进行监测神经元自噬体，线粒体活性氧（ROS），神经元ROS，和线粒体膜电位.Westernblot检测自噬相关蛋白。
结果：在AD小鼠中，HKL改善认知功能，减轻海马Aβ1-42斑块沉积，促进海马神经元存活，并激活海马SIRT3表达和线粒体自噬。通过3-TYP处理消除了HKL对AD小鼠的这些作用。在海马神经元AD模型中，HKL增加神经元活动，减弱神经元凋亡和Aβ聚集，激活的SIRT3和线粒体自噬，减少线粒体和神经元ROS，线粒体膜电位升高.CsA治疗和3-TYP治疗消除了HKL对海马神经元AD模型的保护。HKL对海马神经元AD模型线粒体自噬的促进作用被3-TYP抑制。
结论：HKL激活SIRT3介导的线粒体自噬以减轻AD患者海马神经元损伤。HKL可有效治疗AD。
方法：APP/PS1小鼠作为AD小鼠模型，暴露于HKL和3-TYP。进行Morris水迷宫实验以评估小鼠的认知能力。通过免疫组织化学和Nissl染色评估海马Aβ斑块沉积和神经元存活。海马神经元与C57BL/6小鼠胚胎分离。通过Aβ寡聚体诱导构建海马神经元AD模型，并用HKL处理，CsA和3-TYP。通过细胞计数试剂盒-8测定和TUNEL染色检测神经元活力和凋亡。mRFP-eGFP-LC3测定，MitoSOX红,二氯二氢荧光素二乙酸酯，和JC-1染色进行监测神经元自噬体，线粒体活性氧（ROS），神经元ROS，和线粒体膜电位.Westernblot检测自噬相关蛋白。
结果：在AD小鼠中，HKL改善认知功能，减轻海马Aβ1-42斑块沉积，促进海马神经元存活，并激活海马SIRT3表达和线粒体自噬。通过3-TYP处理消除了HKL对AD小鼠的这些作用。在海马神经元AD模型中，HKL增加神经元活动，减弱神经元凋亡和Aβ聚集，激活的SIRT3和线粒体自噬，减少线粒体和神经元ROS，线粒体膜电位升高.CsA治疗和3-TYP治疗消除了HKL对海马神经元AD模型的保护。HKL对海马神经元AD模型线粒体自噬的促进作用被3-TYP抑制。
结论：HKL激活SIRT3介导的线粒体自噬以减轻AD患者海马神经元损伤。HKL可有效治疗AD。
