讲座题目👫：Alzheimer’s Disease with Comorbidity of Depression: Treatment by targeting phosphodiesterase and signaling mechanisms 主讲人：张汉霆 博士 主持人👩🏿🦲🧭：曹晓华 博士 开始时间◼️：2019-12-13 10:00:00 讲座地址：中北校区脑功能基因组学研究所一楼 主办单位：脑功能基因组学教育部重点实验室
报告人简介➙： 张汉霆博士现为美国西弗吉尼亚大学洛克菲勒神经科学研究所(RNI)终身教授及博士生导师🔖，山东第一医科大学药理学研究所所长🧝🏽♂️、教授，山东省政府“泰山学者海外特聘专家”🐦⬛，山西“百人计划”专家。中国药理学会北美药理学分会常务副主任委员、神经精神药理专业委员会常委👨👨👧👦🧡，美国华人神经科学家学会常务理事,北美药理学会常务理事,中国旅美科技协会总会学术部部长/副会长兼西弗吉尼亚分会/西弗华人协会理事长及名誉会长。张博士毕业于广州南方医科大学(原第一军医大学)医疗系🚣♀️，在军事医学科学院毒物药物研究所先后获得药理学硕士及博士学位。1998年赴美留学👳🏿♀️，先后在美国路易斯安那州立大学和田纳西大学卫生从事神经精神药理学博士后研究👨🚀。张博士在美国20多年来一直从事磷酸二酯酶(PDE)研究。在PDE4对中枢功能的调控方面取得了国际同行公认的成就。先后两次(2006👩🏽，2008)获得美国NARSAD青年科学家奖(NARSAD Young Investigator Award)🙂↕️；并多次担任重要国际会议的主席和／或作大会报告。在国外该领域顶级杂志（包括Journal of Neuroscience， Trends in Pharmacological Sciences和Neuropsychopharmacology）上发表论文及综述100余篇，书稿(篇章) 18部📼。
报告内容： Depression is highly correlated with Alzheimer’s disease (AD), but treatment for the comorbidity of both is lacking. Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP (cAMP), has been considered as a promising target for treatment of both memory loss in AD and depression. Using mouse models of AD, potent PDE4 inhibitors, and PDE4-subtype knockout mice, we demonstrated that PDE4, in particular the PDE4D isoform, plays an important role in the comorbidity of memory loss and depression in AD. Treatment with the PDE4 inhibitor rolipram or roflumilast reversed memory deficits in novel object recognition and Morris water-maze tests in APP/PS1 double transgenic and 3xTg-AD mice, which are widely used models for AD. Similarly, in the tail-suspension and forced-swimming tests, the PDE4 inhibitors reversed the decreased immobility in AD mice, suggesting antidepressant-like effects. The effects of PDE4 inhibitors were mimicked in the tests using mice deficient in PDE4D, which displayed memory-enhancing and antidepressant-like effects, relative to the WT mice microinfused with beta-amyloid peptide 1-42 into the hippocampus. In addition, the PDE4 inhibitor treatment reversed the decreased ratio of Bcl-2/BAX and inhibited the increased expression of PDE4D in the cerebral cortex and hippocampus of AD mice. Further, the PDE4 inhibitors reversed the decreased levels of cAMP and expression of phosphorylated cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) in AD mice. These were mimicked by PDE4D deficiency and treatment with a PDE4D relatively selective inhibitor. In conclusions, these results suggest that PDE4 is an important target for the comorbidity of memory loss and depression in AD, which appears to be mediated by PDE4D-cAMP signaling. |
