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Roles of neural regeneration in memory pharmacology

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Neural Regeneration Research 2018年第3期13卷 406-407页

作者： Miao-Kun Sun blanchette Rockefeller Neurosciences Institute Morgantown WV USA

Neural regeneration, or neuroregeneration, is a brain mechanism essential for rescuing cognitive functions pharmacologically against memory disorders and aging-related memory abnormality. In this short Perspective article, we intend to briefly present the essential roles of neuroregeneration and neural plasticity in learning and memory, memory disorders, and critical involvement in an effective treatment of memory disorders.

关键词： AD Roles of neural regeneration in memory pharmacology

Effect of rifampicin pre-and post-treatment on rotenone-induced dopaminergic neuronal apoptosis and alpha-synuclein expression

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Neural Regeneration Research 2010年第2期5卷 85-91页

作者： Yuanlin Sun Guohua Zhang Jie Xu Shiwen Chen Enxiang Tao Changqing Xu M. Catherine Bennett Department of Neurology Second Affifiated Hospital of Sun Yat-sen University Guangzhou 510120 Guangdong Province China blanchette Rockefeller Neurosciences Institute Rockville MD 20850 USA

BACKGROUND： Rifampicin inhibits the formation of a-synuclein multimer and protects against 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyritine （MPTP）-induced PC12 cell apoptosis. OBJECTIVE： To compare the effect of rifampicin pre- and post-treatment on tyrosine hydroxylase and α-synuclein expression in substantia nigra pars compacta in a rat model of Parkinson＇s disease. DESIGN, TIME AND SE＇B＇ING： A randomized, controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University North Campus （China） from November 2006 to October 2008. MATERIALS： Rifampicin was purchased from MD, USA; rotenone was purchased from Sigma, USA; mouse anti-rat α-synuclein monoclonal antibody was purchased from B＆D, USA; and rabbit anti-rat tyrosine hydroxylase monoclonal antibody was purchased from Chemicon, USA. METHODS： A total of 72 male, Sprague Dawley rats, aged 8 weeks, were randomly assigned to 5 groups： blank control （n = 12）, rifampicin （n = 12）, rotenone （n = 16）, rifampicin pre-treatment （n = 16）, and rifampicin post-treatment （n = 16）. Parkinson＇s disease model rats were established via a subcutaneous injection of rotenone （1.5 mg/kg per day） in the three treatment groups, once a day for 3 successive weeks. Rifampicin （30 mg/kg per day） was intragastrically administered in the rifampicin pre-treatment group 3 days prior to rotenone induction and in the rifampicin post-treatment group 7 days after rotenone induction. Rats were treated with a subcutaneous injection of 1 mL/kg per day sunflower oil in the blank control group and an intragastric injection of 30 mg/kg per day rifampicin in the rifampicin group, once a day for 3 successive weeks in total. MAIN OUTCOME MEASURES： Prior to treatment and in the end of the 3^rd week after treatment, the rats were evaluated using the modified neurological severity score. The substantia nigra from the rats was extracted for hematoxylin-eosin staining. Western blot analysis was performed to determine tyrosine hydroxyla

关键词： rifampicin rotenone Parkinson's disease α-synuclein dopaminergic neurons

Synergistic facilitation of Bryostatin-1 and Vitamin E on classical conditioning of the rabbit （Oryctolagus cuniculus） nictitating membrane response

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Synergistic facilitation of Bryostatin-1 and Vitamin E on cl...

阿尔茨海默病的药物治疗靶点及新药研发进展:我们还有新武器吗?

第十五届国际药理学大会

作者： Darwish Deya Schreurs Bernard G blanchette Rockefeller Neurosciences Institute West Virginia University School of Medicine5700 HSS PO Box 9302Medical Center Drive Morgantown WV 26506 Department of Physiology and Pharmacology and blanchette Rockefeller Neurosciences Institute West Virginia University School of Medicine 5700 HSS PO Box 9302 Medical Center Drive Morgantown WV 26506

＜正＞ Our previous work has demonstrated that protein kinase C （PKC） is involved in classical conditioning. This study was to investigate if PKC modulator. Bryostatin - 1,was capable of facilitating rabbit conditioned NMR;and if there was a synergisticeffect between Bryostatin - 1 and Vitamin E. Bryostatin - 1 showed a dose - dependent increase in conditioned eyeblink responses from the fifth trace day. Compared to the paired rabbits receiving vehicle. Bryostatin - 1 alone, paired animals receiving both 10μg/kg Bryostatin - 1 and Vitamin E exhibited significantly more conditioned eyeblink responses. Bryostatin - 1 did not alter the reactivity to airpuff （US） and tone （CS）. These findings demonstrate a strong synergisticeffect on rabbit conditioned nictitating membrane responses between Bryostatin - 1 and Vitamin E and suggest Bryostatin - 1 and Vitamin E may be an optional treatment for learning disabilities and memory deficits in clinics.

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中国药理学与毒理学杂志 2017年第7期31卷 701-706页

作者：胡薇薇侯雪芹廖儒佳张汉霆浙江大学医药学部浙江杭州310058 齐鲁医科大学(筹)药理学研究所山东泰安271016 Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology Blanchette Rockefeller Neurosciences InstituteWest Virginia University Health Sciences Center

阿尔茨海默病(AD)是一种慢性进行性神经系统变性疾病,为最常见的痴呆类型,其发病率逐年增加,目前已是继心血管疾病和肿瘤之后导致老年人死亡的第三大病因。由于AD的发病机制至今尚未完全明确,因此,抗AD相关药物研发进展缓慢,其前景不容... 详细信息

阿尔茨海默病(AD)是一种慢性进行性神经系统变性疾病,为最常见的痴呆类型,其发病率逐年增加,目前已是继心血管疾病和肿瘤之后导致老年人死亡的第三大病因。由于AD的发病机制至今尚未完全明确,因此,抗AD相关药物研发进展缓慢,其前景不容乐观。发展有效的抗AD药物成为当前AD研究领域的热点和难点。近日,由海内外众多神经精神药理研究领域的华人科学家组成的"神经精神科学微信群"就此进行了热烈的讨论。专家们指出,对AD主流病理假说的误导以及目前抗AD药物筛选平台的问题均可导致新药开发的误区。我们应从整体观、大数据的角度重新审视AD病理及治疗策略,寻找多靶点全方位的综合治疗手段,并可根据AD病理过程的更上游因素将病程分型。此外,AD患者脑内线粒体的损伤和功能障碍,长期暴露于低剂量电离辐射造成AD样的病理改变等,为AD的发病机制和防治策略提供新的视角和思路。

关键词：阿尔茨海默病靶点新药研发

建立啮齿类酒精饮用动物模型的影响因素及研究进展

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中国药理学与毒理学杂志 2017年第6期31卷 607-614页

作者：刘欣张倩倩王圣霞张旺信张汉霆泰山医学院药理学研究所山东泰安271000 泰山医学院基础医学院医学心理学教研室山东泰安271000 泰山医学院脑科研究所山东泰安271000 泰安市中心医院眼科山东泰安271000 Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology Blanchette Rockefeller Neurosciences InstituteWest Virginia University Health Sciences Center

酒精使用障碍(AUD)是威胁人类健康乃至生命的重要因素之一。世界卫生组织数据显示,全球每年因AUD而死亡的人数约330万。AUD已成为一个全球性公共卫生和社会性问题,但其神经行为学机制并未完全阐明。因此,建立有效和可靠的酒精饮用动物... 详细信息

酒精使用障碍(AUD)是威胁人类健康乃至生命的重要因素之一。世界卫生组织数据显示,全球每年因AUD而死亡的人数约330万。AUD已成为一个全球性公共卫生和社会性问题,但其神经行为学机制并未完全阐明。因此,建立有效和可靠的酒精饮用动物模型对AUD机制的探讨非常重要。本文从动物品系和造模方法等方面进行综述,探讨可能对造模结果造成偏差的相关影响因素,以期对AUD的动物行为学研究有所裨益。

关键词：酒精动物品系饮酒模型啮齿类动物

Phosphodiesterases:novel targets for treatment of alcoholism

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中国药理学与毒理学杂志 2017年第5期31卷 454-455页

作者： LIU Xin WEN Rui-ting GONG Mei-fang XU Ying Nicolas GRAHAME XU Jiang-ping LIANG Jian-hui Marco CONTI 张汉霆 Institute of Pharmacology Taishan Medical University Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology Blanchette Rockefeller Neurosciences InstituteWest Virginia University Health Sciences Center Department of Molecular and Cellular Pharmacology School of Pharmaceutical SciencesPeking University Department of Pharmacology School of Pharmaceutical SciencesSouthern Medical University Department of Pharmaceutical Sciences State University of New York at Buffalo Department of Psychology Indiana University-Purdue University Indianapolis Center for Reproductive Sciences Department of ObstetricsGynecology and Reproductive SciencesUniversity of California 泰山医学院药理学研究所泰山医学院药学院美国西弗吉尼亚大学医学院中国旅美科技协会西弗吉尼亚分会美国西弗吉尼亚华人协会

OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in ***(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol ***,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by *** The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcohol

关键词： phosphodiesterase alcohol drinking alcoholism anxiety depression rodents

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磷酸二酯酶:从伟哥到抗阿尔茨海默病药物

中国药理学与毒理学杂志 2019年第10期 790-790页

作者：王浩周延萌侯雪芹张芳芳赵晓民张汉霆山东第一医科大学山东省医学科学院药理学研究所 Departments of Neuroscience and Behavioral Medicine & Psychiatry Blanchette Rockefeler Neurosciences InstituteWest Virginia University Health Sciences Center

磷酸二酯酶（PDE）是一个催化第二信使c AMP和/或c GMP水解的超级酶家族。它包括11个家族（PDE1～PDE11）,对调节细胞内cAMP和cGMP水平发挥关键作用。PDE研究半个世纪以来,其靶位功能越发明显并受到重视。尤其是靶位PDE5的伟哥（Viagra,... 详细信息

磷酸二酯酶（PDE）是一个催化第二信使c AMP和/或c GMP水解的超级酶家族。它包括11个家族（PDE1～PDE11）,对调节细胞内cAMP和cGMP水平发挥关键作用。PDE研究半个世纪以来,其靶位功能越发明显并受到重视。尤其是靶位PDE5的伟哥（Viagra,sildenafil;PDE5抑制剂）研制成功,使PDE研究成为国际药物研发的一大热点。PDE4抑制剂罗氟司特（roflumilast,Daxas;）和apremilast（Otezla;）分别成功用于治疗慢性阻塞性肺疾患（COPD）和银屑病及银屑病性关节炎,再次证明PDE作为药物靶标的重要研究价值和临床应用前景。阿尔茨海默病（AD）是一种慢性进行性神经退行性疾病,以记忆和认知能力的进行性减退为主要临床特征。研究表明,PDE2,PDE4,PDE5,PDE7,PDE9和PDE11都不同程度地参与AD学习记忆和认知的调节,其中尤以PDE4作用明显而广泛。PDE4有4种亚型（PDE4A～D）,由不同基因编码。PDE4D研究相对较多。基因敲除或敲减PDE4D可改善AD小鼠的学习记忆障碍及抑郁等行为;对PDE4D有选择性抑制作用的化合物也有类似作用,提示PDE4D可能是治疗AD的重要靶标。然而,PDE4D也参与中枢性呕吐作用的调节。最新研究表明,通过别构抑制PDE4D可以达到既对抗AD小鼠的记忆下降,又不至于产生呕吐等副反应。这可能是抗AD药物研究的一个重要方向。

关键词：磷酸二酯酶阿尔茨海默病记忆抑郁抑制剂