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镇学初

镇学初教授:苏州大学药学院院长、药理学系教授、博士生导师,中科院“百人计划”及国家杰出青年基金获得者。1996 年获瑞士日内瓦大学博士学


镇学初镇学初

位。
 1996-1999 年于宾西法尼亚州立大学医学院及宾西法尼亚医学院药理学系进行博士后研究。2000-2002年担任美国费城Drexel医学院药理系助理教授。2003-2006年担任美国纽约城市大学医学院药理与生理学系副教授。2006年任中国科学院上海药物所研究员、神经递质课题组组长。主要从事精神神经药理研究及相关药物研发,发表SCI论文60余篇。申请中国专利13,
授权2项。合作主编“脑内多巴胺”学术专著。学术兼职有中国药理学会神经精神专业委员会副主委,中国神经科学学会理事,上海神经科学学会理事。并担任APS, Frontier Neurosci.; AMJBS编委。先后主持科技部863,国家杰出青年科学基金、国家自然科学基金、国家重大专项新药创制项目,作为骨干先后参加多个973项目。
 
研究方向
1.   靶向神经精神重大疾病的药物研发:以精神分裂症、帕金森氏病、抑郁症、药物成瘾为靶向,寻找和发现新型小分子药物。
2.   神经递质受体调控及信号传导机制:研究神经递质特别是多巴胺受体信号及功能调控的分子机制,并探讨其在重大神经精神疾病中的作用和机理。
3.   胶质细胞及神经免疫:研究胶质细胞功能调控的机制,及其在生理病理条件下的作用,神经免疫与胶质功能调控。
 
主要代表性论文
学术专著:《脑内多巴胺》,上海科技出版社,主编:金国章,镇学初,2010.9
  
Invited Reviews
1.        Chu HY, Zhen X*. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels in the regulation of midbrain dopamine systems. Acta Pharmacol Sin. 2010 Sep; 31(9):1036-43.
2.       
2.        Zhang J, Xiong B, Shen JK, Zhen X, Zhang A. Dopamine D1 Receptor Ligands: Where are we now and where are we going? Med. Res. Rev. 2009 Mar; 29(2):272-94.
3.        Chu HY, Jin GZ, Friedman E, Zhen X*. Recent Development in Studies of Tetrahy droprotoberberines: Mechanism in Antinociception and Drug Addiction. Cell Mol Neurobiol. 2008 Jun; 28(4):491-9.
4.        Mo J, Guo Y, Yang YS, GZ Jin, Zhen X*. A novel dual dopamine D1 receptor agonist and D2 receptor antagonist: potential antipsychotic agents. Current Medical Chemistry. 2007, 14:2996-3002.
 

Research Papers (Selected):

(1)   Chu HY, Wu Q, Zhou S, Cao X, Zhang A, Jin GZ, Hu GY, Zhen X. SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism. J Neurosci Res. 2011 May 2. doi: 10.1002/jnr.22653. [Epub ahead of print]

(2)   Mao X, Wang Y, Carter AV, Zhen X, Guo SW. The Retardation of Myometrial Infiltration, Reduction of Uterine Contractility, and Alleviation of Generalized Hyperalgesia in Mice With Induced Adenomyosis by Levo-Tetrahydropalmatine (l-thp) and Andrographolide. Reprod Sci. 2011 Apr 14. [Epub ahead of print]

(3)   Ye N, Wu Q, Zhu L, Zheng L, Gao B, Zhen X, Zhang A. Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D(3) receptor ligands. Bioorg Med Chem. 2011 Mar 15; 19(6):1999-2008.

(4)   Chu HY, Yang Z, Zhao B, Jin GZ, Hu GY, Zhen X*. Activation of phosphatidylinositol-linked D1-like receptors increases spontaneous glutamate release in rat somatosensory cortical neurons in vitro.Brain Res. 2010 Jul 9; 1343:20-7.

(5)   Mo J, Zhang H, Yu LP, Sun PH, Jin GZ, Zhen X. L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. Neurobiol Aging. 2010 Jun; 31(6):926-36.

(6)   Chu HY, Zhen X. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels in the regulation of midbrain dopamine systems. Acta Pharmacol Sin. 2010 Sep; 31(9):1036-43.

(7)   Chu HY, Gu QH, Jin GZ, Hu GY, Zhen X*. Electrophysiological Effects of SKF83959 on Hippocampal CA1 Pyramidal Neurons: Potential Mechanisms for the Drug’s Neuroprotective Effects. PlosOne. 2010 Oct 1; 5(10): e13118.

(8)   Gao MChu HYJin GZZhang ZJWu J, Zhen X*. l-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental area is associated with its 5-HT(1A) receptor partial agonistic activity. Synapse.2011 May; 65(5):379-87.

(9)   Zhao TLiu X, Zhen X*, Guo SWLevo-Tetrahydropalmatine (l-THP) Retards the Growth of Ectopic Endometrial Implants and Alleviates Generalized Hyperalgesia in Experimentally Induced Endometriosis in Rats. Reprod Sci. 2011 Jan; 18(1):18-45.

(10)   Wu C, Yang K, Liu Q, Wakui M, Jin GZ, Zhen X*, Wu J. Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons acutely-dissociated from rat substantia nigra pars compacta. Neuropharmacology. 2010 Dec; 59(7-8):567-72.

(11)   LiuZZhang H, Yu LP, Zhen X*, Zhang A. Synthesis of Furo[3,2-l]aporphine and Dihydrofuro[3,2-l]aporphine Derivatives: Identification of a Potent and Selective 5-HT1A Receptor Agonist. J. Med. Chem. 2010 Feb 11; 53(3):1319-28.

(12)   Zhang J, Zhang H, Cai W, Yu L, Zhen X*, Zhang A. 'Click' D(1) receptor agonists with a 5-HT(1A) receptor pharmacophore producing D(2) receptor activity. Bioorg Med Chem.2009 Jul 15; 17(14):4873-80.

(13)   Zhang X, Fei Ding, Zhen X*, Jiawei Zhou. PI-linked D1 receptor-Mediated FGF-2 Expression in Astrocytes Protects Dopaminergic Neurons. J. Neurosci. 2009, 29(24):7766-75.

(14)   Guo Y, Zhang H, Chen X, Cai W, Cheng J, Yang Y, Jin G, Zhen X*. Evaluation of the a antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand. Schizophrenia Res. 2009 Nov; 115(1):41-9.

(15)   Sun P, Wang J, Gu W, Cheng W, Jin GZ, Friedman E, Zheng J, Zhen X*. PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation. Cell Res. 2009 May; 19(5):612-24.

(16)   Chen XQ, Zhang J, Neumeyer JL, Jin GZ, Hu GY, Zhang A, Zhen X*. Arylbenzazepines are potent modulators for the delayed rectifier K+ channel: a potential mechanism for their neuroprotective effects. PLoSOne. 2009 Jun 5; 4(6):e5811.

(17)   Yang K, Hu J, Lucero L, Liu Q, Zheng C, Zhen X*, Jin G, Lukas RJ, Wu J. Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons. J Physiol. 2009 Jan 15; 587(Pt 2):345-61.

(18)   Liu Z, Chen X, Yu L, Zhen X*, Zhang A. Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines. Bioorg Med Chem. 2008 Jul 15; 16(14):6675-81.

(19)   Liu Z, Chen X, Sun P, Yu L, Zhen X, Zhang A. N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D(2) and serotonin 5-HT(1A) receptor dual ligands. Bioorg Med Chem. 2008 Sep 15; 16(18):8335-8.

(20)   Zhang D, Zhang H, Jin GZ, Zhang K, Zhen X*. Single dose of morphine produced a prolonged effect on dopamine neuron activities. Mol Pain. 2008 Nov 17; 17: 4-57.

(21)   Zhang D,  Yang S,  Yang C,  Jin G,  Zhen X*. Estrogen modulated cocaine-altered dopamine neuron activity in ventral tegmental area. Psychopharmacology. 2008, 199(4):625-35.

(22)   Mo J, Zhang H, GZ Jin, Zhen X*. SPD attenuated L-DOPA-induced dyskinesia in Parkinsons disease rat model. Neurobiolgy of aging. 2010 Jun; 31(6):926-36.

(23)   Zhang J, Chen X, Yu L, Zhen X*, Zhang A. Synthesis of 6-substituted 1-phenylbenzazepines and their dopamine D(1) receptor activities. Bioorg Med Chem. 2008 Nov1; 16(21):9425-31.

(24)   Feng YQ, Zhou ZY, He X, Wang H, Guo XL, Hao CJ, Guo Y, Zhen X, Li W. Dysbindin deficiency in sandy mice causes reduction of snapin and displays behaviors related to schizophrenia.Schizophr Res. 2008 Dec; 106(2-3):218-28.

(25)   Zhang ZJ, Tan QR, Tong Y, Li Q, Kang WH, Zhen X, Post RM. The effectiveness of carbamazepine in unipolar depression: a double-blind, randomized, placebo-controlled study. J Affect Disord. 2008 Jul; 109(1-2):91-7.

(26)   Yu Y, Wang JR, Sun PH, Guo Y, Zhang ZJ, Jin GZ, Zhen X*. Neuroprotective effects of atypical D1 receptor agonist SKF83959 are mediated via D1 receptor-dependent inhibition of glycogen synthase kinase-3beta and a receptor-independent anti-oxidative action. J Neurochem. 2008 Feb; 104(4):946-56.

(27)   Gu WH, Yang S, Shi WX, Jin GZ, Zhen XC. Requirement of PSD-95 for dopamine D1 receptor modulating glutamate NR1a/NR2B receptor function. Acta Pharmacol Sin. 2007 Jun; 28(6):756-62.

(28)   Tan QR, Wang XZ, Wang CY, Li XJ, ChenY,Wang HHZhen X and Zhang ZJ. Differential effects of atypical and classical antipsychotics in protecting against neurotoxicity induced by rotenone in PC12 cells.  Eur Neuropsychopharmacol. 2007, 17(12):768-73.

(29)   Zhen X, Goswami S, Abdali SA, Frankfurt M, Friedman E. Estrogen-modulated frontal cortical CaMKII activity and behavioral supersensitization induced by prolonged cocaine treatment in female rats. Psychopharmacology (Berl). 2007 Apr; 191(2):323-31.

(30)   Zhang H, Wang F, Chen J, Zhen X*. SKF83959 attenuated L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson’s disease. Neuropharmacology. 2007 Jul; 53(1):125-33.

(31)   Mo J, Guo Y, Yang YS, Shen JS, Jin GZ, Zhen X. Recent developments in studies of l-stepholidine and its analogs: chemistry, pharmacology and clinical implications. Curr Med Chem. 2007, 14(28):2996-3002.

(32)   GU W, Shi WX, Zhen X,  Jin G. Effects of (-) -stepholidineon NMDA receptors comparison with haloperidol and clozapine. Acta Pharmacologica Sinica. 2007 Jul; 28(7):953-8.

(33)   Gu W, Shi WX,  Jin G, Zhen X*. Requiring PSD-95 for Ddopamine receptor modulating NMDA receptor function. Acta Pharmacologica Sinica. 2007, 28(6):756-62.

(34)   Gao M, Liu CL, Yang S, Zhen X, Jin GZ. l-Stepholidine increases the frequency of sEPSC via the activation of D1 dopamine signaling pathway in rat prelimbic cortical neurons. Acta Pharmacol Sin.2007 May; 28(5):627-33.

(35)   Ming Y, Zhang H, Long L, Wang F, Chen J, Zhen X. Modulation of Ca2+ signals by phosphatidylinositol-linked novel D1 dopamine receptor in hippocampal neurons. J Neurochem. 2006 Aug; 98(4):1316-23.

(36)   Zhen X*, S Gaswomi, E Friedman. Estrogen-modulated frontal cortical CaMKII activity is involved in behavioral supersensitization to cocaine in female rats. Psychopharmacology. 2007 Apr; 191(2):323-31.

(37)   Yuling Ming, Hai Zhang, J Chen, Zhen X*. SKF83959 stimulates Ca2+ signaling in primary cultured hippocampal neurons. J. Neurochem. 2005, 98:1316-23.

(38)   Zhang-Jin Zhang, Xiao-Long Jiang, Steven E. Zhang, Yan Zhang, Christopher J. Hough, He Li, Zhen X*. The paradoxical effects of SKF83959, a novel dopamine D1-like receptor agonist, in the rat acoustic startle reflex paradigm. Neurosci. Lett.2005 Jul; 382(1-2):134-8.

(39)   Zhen X*, Satindra Goswami. Activation of Phosphatidyinositol (PI)-linked D1 Dopamine Receptor Is Associated With The Antiparkinsonian Action of SKF83959. Biochem. Pharm. Behav. 2005, 80(4):597-601.

(40)   Zhen X*, Gaswomi S, abdali SA. Regulation of cdk5 and CaMKII by PI-linked dopamine receptor in rat brain. Mol Pharmacol. 2004 Dec; 66(6):1500-7.

(41)   M Gil, Zhen X*. Prenatal cocaine exposure alters GSK3β pathways in select rabbit brain areas.Neurosci Lett. 2003 Oct 9; 349(3):143-146.

(42)   LQ Jin, Gaswami S, Zhen X*. SKF83959 selectively regulates phosphatidylinositol-linked D1 dopamine receptors in rat brain. J. Neurochem. 2003 Apr; 85(2):378-86.

(43)   Zhen X*, C Torries, GP Cai, et al. Inhibition of striatal protein tyrosine phosphatases is associated with D2 dopamine receptor-mediated  supersensitivity in  Parkisno’s rat model. Mol. Pharmacol.2002, 62:1356-1362.

(44)   Zhen X*, C Torries, E Friedman. Lithium regulates tyrosine phosphatase activity in vivo and in vitro. Psychopharm. 2002 Aug; 162(4):379-84.

(45)   Zhen X*, Claudio Torres, Hoau-Yan Wang. Prenatal exposure to cocaine disrups D1A dopamine receptor function via selective inhibition of protein phosphatase 1 pathway in rabbit frontal cortex. J. Neurosci. 2001 Dec 1; 21 (23): 9160-67.

(46)   Zhen X*, J Zhang, E Friedman. D4 dopamine receptor differentially regulates Akt/NF-kB pathways in D4MN9D cells. Mol.Pharmacol. 2001 Oct; 60(4):857-64.

(47)   J Yu, Reilly G, Zhen X, CE Yellowley, CR Jacobs. Osteopontin gene regulation by oscillatory fluid flow via intracellular calcium mobilization and activation of mitogen-activated protein kinase in MC3T3-E1 cells. J. Biol. Chem. 2001 Apr 20; 276(16):13365-13371.

(48)   Zhen X*, W Du, R Anthony, E Friedman and J Harvey. The p38 MAPK is involved in associative learning in rabbits. J. Neurosci. 2001 Aug 1; 21(15): 5513-9.

(49)   Zhen X*, Wu Q and Q Chen. Role of p38 MAPK in PTH-regulated chondrocyte differentiation.J. Biol. Chem. 2001, 276:4879-85.

(50)   Zhen X, GP Cai (co-first author), K Uryu, E Friedman. Activation of extracellular signal-regulated protein is associated with sensitized locomotive response to D2 dopamine receptor stimulation in unilateral 6-hydroxydopamine-lesioned rats. J. Neurosci. 2000 Mar 1; 20(5):1849-1857.

(51)   Zhen X, K Uryu, GP Cai, J Johnson, E Friedman. Age-related impairment of MAP kinase and effect of caloric restriction in brains of Fisher 344 rats.  J. Gerontol. 1999, 54A:B539-548.

(52)   Zhen X, K Uryu, HY Wang and E Friedman. D1 dopamine receptor agonists mediate activation of p38 MAPK and JNK by a protein Kinase A-dependent mechanism in SK-N-MC cells. Mol. Pharmacol. 1998 Sep, 54(3):453-458.

(53)   Zhen X, JP Bonjour and J Caverzasio. Platelet-derived growth factor stimulates sodium-dependent Pi transport in osteoblastic cells via phospholipase Cg and phosphatidylinositol 3’kinase. J. Bone & Mineral Res. 1997, 12:35-42 . 
(54)   Imai, Zhen X, JP Bonjour and J Carverzasio. Aluminum potentiates Pi transport stimulation induced by fluoride in osteoblast-like cells. Am. J. Physiol. 1996, 271(Endocrinol. Metab.34): E694-701.

  
E-mail: zhenxuechu@suda.edu.cn

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