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熊志奇

熊志奇,1968年8月生,博士,研究员。现任中国科学院脑科学与智能技术卓越中心高级研究员;中科院脑科学卓越创新中心脑疾病机理研究部负责人;1992年本科毕业于华西医科大学;1995年中科院上海药物研究所硕士毕业;2000年获贝勒医学院博士学位;2000-2003年杜克大学神经生物学系博士后;2003年至今任中科院神经科学研究所,研究员、博士生导师。

    主要研究方向及内容

    神经系统疾病是一类发病率较高的疾病,中风、癫痫、早老性痴呆等常见的神经系统疾病影响全球数千万人的健康,加上一些较为罕见的疾病如雷特综合征、Rasmussen脑炎等,已经成为日益严重的医疗负担和社会问题。虽然目前已有一些手段及方法应用于某些神经系统疾病的临床诊断和治疗,但基于发病机制研究的、用于预防或治愈这类神经系统疾病的方案依旧匮乏。本研究组的长期研究方向是了解这些神经系统疾病在细胞和分子水平的发病机理,其中特别关注儿童智力发育障碍疾病和癫痫病的研究。

    1.智力障碍的分子和遗传机制  

    智力发育障碍(mental retardation),又称为精神发育不全或弱智,是儿童期最常见的神经系统疾病之一。引起智力障碍的原因可以是遗传性的,如多基因或单基因突变;也可以是非遗传性的,如神经系统感染,药物滥用,或脑损伤。其主要症状是智力发育迟缓,适应能力低下,注意力不集中等。部分病人(20-30%)伴随有癫痫发作。智力障碍的发病率约为2-3% 。在欧洲,约有8% 的医疗费用于智力疾病的治疗,远远高于其他同类疾病的费用。因此,智力障碍疾病成为医学领域中最重要的有待解决的难题之一。X 性染色体连锁 (X-linked mental retardation)的基因功能缺陷是智力发育迟缓的主要病因。它包括脆性X综合症(Fragile X mental retardation), 雷特综合征(Rett Syndrome)和安吉尔曼综合征(Angelman Syndrome)等。目前已鉴定出一些基因与智力障碍相关,如脆性 X 综合症中的 fmr1 基因,雷特综合征中的 mecp2 基因和 stk9 基因,以及安吉尔曼综合征中的 ube3a 基因等,并且在实验小鼠模型中已证明这些基因突变影响神经系统发育和学习记忆。但这些基因突变如何导致智力障碍的分子机理尚不明确。小鼠的整体基因敲除会引起一系列的发育异常、代谢变化和突触联系改变等反应,导致难以建立突变基因与相应症状的直接联系。因此我们的策略为:在小鼠中,选择性的在特定脑区敲除与智力障碍疾病相关的基因,通过分析突触可塑性、学习记忆和癫痫发生等指标研究这些基因的功能;并且,小鼠特定脑区中在单个神经元水平敲除与智力障碍疾病相关的基因,并且使该神经元可视化,从而研究这些基因在神经元形态学、发育和可塑性中的作用。

    2.癫痫病发生的分子机制  

    癫痫的发病率约在 1-2%,在儿童中比例更高。大约 35%-40% 癫痫病儿童同时也伴有智力障碍。脑损伤如中风、脑外伤、高烧惊厥、脑膜炎、脑炎或相关的发育疾病均可引起癫痫的发生。癫痫发生机制尚不清楚,目前也无有效的预防措施和彻底治疗手段。现有药物只能缓解癫痫的症状,而不能根除病灶。癫痫发作的特征是神经元活动的高兴奋性和高同步性,这种神经元的异常行为一般认为是正常功能的脑组织受到损伤后导致的永久性的可塑性变化。通过在分子水平对癫痫发生机制的研究,可以为癫痫的临床治疗提供新的方案和药物作用靶点。同时癫痫的产生伴随着神经可塑性、兴奋性的变化,以及神经元的损伤、修复和再生,所以通过对癫痫机制的研究还可以对其他神经退行性病变提供间接的理论解释,并有助于我们对脑功能的进一步深入了解。癫痫常伴有神经元的退行性损伤。已有研究表明,过度激活 NMDA 受体可引起神经元凋亡,但癫痫发生和神经退行性病变之间的因果关系,以及 NMDA 受体拮抗剂的抗癫痫作用是否来自其神经保护作用等问题仍备受争议。NMDA 受体有不同亚型,因此我们将研究 NMDA 受体的不同亚型在癫痫发生中的作用。

    3.非人灵长类疾病模型的建立  

    相比其他动物模型,非人灵长类动物与人类在代谢免疫、解剖和基因网络上具有更大的相似性。我们所的灵长类平台已经成功掌握了克隆猴技术,如果结合新的基因编辑技术,就可以构造各种类型的遗传修饰的神经疾病猴模型。这些模型将大大促进脑神经疾病机理的研究。而对这些疾病猴模型发病周期的各种代谢物、免疫组、脑影像学、神经环路功能和行为学等方面的研究,将极大的推动早期诊断生物标记物的发现和应用,并进而促进神经疾病的药物治疗和物理干预研发。我们正与各个平台合作,建立遗传性神经疾病的猴模型(阿尔滋海默氏症、帕金森氏症和智力发育障碍克隆猴)和甲基苯丙胺成瘾和强迫症猕猴模型,并基于这些模型开展认知行为评价范式、在体电生理记录和物理干预手段研发的研究。

    代表性论文

    Wang T, Wang J, Wang J, Mao L, Tang B, Vanderklish PW, Liao X, Xiong ZQ and Liao L. (2019)HAP1 is an in vivo UBE3Atarget that augments autophagy in a mouse model of Angelman syndrome. Neurobiol Dis., 2019 Dec; 132:104585.

    Lin X, Su HZ, Dong EL, Lin XH, Zhao M, Yang C, Wang C, Wang J, Chen YJ, Yu H, Xu J, Ma LX, Xiong ZQ, Wang N, Chen WJ. Stop-gain mutations in UBAP1 cause pure autosomal-dominant spastic paraplegia. Brain. 2019 Jun 15. pii: awz158.

    Wang J, Lou SS, Wang T, Wu RJ, Li G1, Zhao M, Lu B, Li YY, Zhang J, Cheng X, Shen Y, Wang X Zhu ZC, Li MJ, Takumi T, Yang H, Yu X, Liao L, Xiong ZQ. UBE3A-mediated PTPA ubiquitination and degradation regulate PP2Aactivity and dendritic spine morphology. PNAS. 2019  Jun 18;116(25):12500-12505.

    Zhu ZC, Liu JW, Yang C, Zhao M, Xiong ZQ. XPO1 inhibitor KPT-330 synergizes with Bcl-xL inhibitor to induce cancer cell apoptosis by perturbing rRNA processing and Mcl-1 protein synthesis. Cell Death Dis. 2019 May 21;10(6):395.

    Zhu ZC, Liu JW, Yang C, Li MJ, Wu RJ, Xiong ZQ. Targeting KPNB1 overcomes TRAIL resistance by regulating DR5, Mcl-1 and FLIP in glioblastoma cells. Cell Death Dis. 2019 Feb 11;10(2):118.

    Zhu YC and Xiong ZQ. (2019) Molecular and synaptic bases of CDKL5 disorder. Dev. Neurobiol. 79: 8-19.

    Yao XP, Cheng X, Wang C, Zhao M, Guo XX, Su HZ, Lai LL, Zou XH, Chen XJ, Zhao Y, Dong EL, Lu YQ, Wu S, Li X, Fan G, Yu H, Xu J, Wang N, Xiong ZQ, Chen WJ.( 2018 )Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification. Neuron. 98(6):1116-1123.

    Zhu ZC, Liu JW, Li K, Zheng J, Xiong ZQ.(2018) KPNB1 inhibition disrupts proteostasis and triggers unfolded protein response-mediatedapoptosis in glioblastoma cells.Oncogene.37(22):2936-2952

    Tan GH, Liu YY, Wang L, Li K, Zhang ZQ, Li HF, Yang F, Li Y, Li D, Wu MY, Yu CL, Long JJ, Chen RC, Li LX, Yin LP, Liu JW, Cheng XW, Shen Q, Shu YS, Sakimura K, Liao LJ, Wu ZY and Xiong ZQ*. (2018) PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum. Cell Res. 28(1):90-110.

    Zuo, E., Cai, Y., Li, K., Wei, Y., Wang, B., Sun, Y., Liu, Z., Liu, J., Hu, X., Wei, W., Huo, X., Shi, L., Tang, C., Liang, D., Wang, Y., Nie, Y., Zhang, C., Yao, X., Wang, X., Zhou, C., Ying, W., Wang, Q., Chen, R., Shen, Q., Xu, G., Li, J., Sun, Q.*, Xiong, ZQ* and Yang, H.* (2017)  One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs. Cell Res. 27: 933-945.

    Yang Z, Li PF, Chen RC, Wang J, Wang S, Shen Y, Wu XH, Fang B, Cheng XW, Xiong ZQ (2017) ADAM10-initiated release of Notch intracellular domain regulates microtubule stability and radial migration of cortical neurons.  Cerebral Cortex. 27(2):919-932.

    Li W, Yao A, Zhi H, Kaur K, Zhu YC, Jia M, Zhao H, Wang Q, Jin S, Zhao G, Xiong ZQ and Zhang YQ. (2016) Angelman Syndrome Protein Ube3a Regulates Synaptic Growth and Endocytosis by Inhibiting BMP Signaling in Drosophila. PLoS Genet. 12(5):e1006062.

    Xiong H, Cassé F, Zhou M, Xiong ZQ, Joels M, Martin S and Krugers HJ. (2016) Interactions between N-Ethylmaleimide-Sensitive Factor and GluA2 contribute to effects of glucocorticoid hormones on AMPA receptor function in the rodent hippocampus. Hippocampus. 26: 848-856.

    Poo MM,  Du JL, Ip NY, Xiong ZQ, Xu B, Tan T. (2016) China Brain Project: Basic Neuroscience, Brain Diseases, and Brain-Inspired Computing. Neuron. 92: 591-596.  

    Zhang Q, Zhang Y, Wang C, Xu Z, Liang Q, An L, Li J, Liu Z, You Y, He M, Mao Y, Chen B, Xiong ZQ, Rubenstein JL and Yang Z. (2016) The Zinc Finger Transcription Factor Sp9 Is Required for the Development of Striatopallidal Projection Neurons. Cell Rep. 16:1431-1444.

    Liu Z, Li X, Zhang JT, Cai YJ, Cheng TL, Cheng C, Wang Y, Zhang CC, Nie YH, Chen ZF, Bian WJ, Zhang L, Xiao J, Lu B, Zhang YF, Zhang XD, Sang X, Wu JJ, Xu X, Xiong ZQ, Zhang F, Yu X, Gong N, Zhou WH, Sun Q and Qiu Z. (2106) Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2. Nature. 530: 98-102.

    Li Y, Wang J, Zhou Y, Li D and Xiong ZQ. (2015) Rcan1 deficiency impairs neuronal migration and causes periventricular heterotopia. J. Neurosci. 35(2): 610-620.

    Xiong H, Cassé F, Zhou Y, Zhou M, Xiong Z-Q, Jo?ls M, Martin S, and Krugers HJ. (2015) mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory. Learn Mem. 22: 577-583.

    Wang HT, Zeng L, Chen Q, Zhang X, Liu JW, Lu TJ, Xiong ZQ, Zheng J and Hu ZL. (2015) β-Catenin is required for maintaining hippocampal morphology during the perinatal period. Neuroscience. 284: 273-282.

    Liu ZJ, Li HF, Tan GH, Tao QQ, Ni W, Cheng XW, Xiong ZQ and Wu ZY. (2014) Identify mutation in amyotrophic lateral sclerosis cases using HaloPlex target enrichment system. Neurobiol. Aging. 35: 2881.e11-5.

    Li K, Liu JW, Zhu ZC, Wang HT, Zu Y, Liu YJ, Yang YH, Xiong ZQ, Shen X, Chen R, Zheng J and Hu ZL. (2014) DSTYK kinase domain ablation impaired the mouse capabilities of learning and memory in water maze test. Int J Clin Exp Pathol. 7: 6486-6492.

    Lu T, Chen R, COX TC, Moldrich RX, Kurniawan N, Tan G, Perry JK, Ashworth A, Bartlett PF, Xu L, Zhang J, Lu B, Wu M, Shen Q, Liu Y, Richards LJ and Xiong ZQ. (2013) X-linked microtubule-associated protein, Mid1, regulates axon development. Proc. Natl. Acad. Sci. USA. 110: 19131-19136. 

    Zhu YC, Li D, Wang L, Lu B, Zheng J, Zhao SL, Zeng R and Xiong ZQ. (2013)  Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development. Proc. Natl. Acad. Sci. USA. 110:  9118-9123.

    Li K, Zhu ZC, Liu YJ, Liu JW, Wang HT, Xiong ZQ, Shen X, Hu ZL and Zheng J. (2013) ZFX knockdown inhibits growth and migration of non-small cell lung carcinoma cell line H1299. Int J Clin Exp Pathol. 6: 2460-2067.

    Li FH, Chen WJ, Ni W, Wang KY, Liu GL, Wang N, Xiong ZQ, Xu J and Wu ZY (2013) PRRT2 mutation correlated with phenotype of paroxysmal kinesigenic dyskinesia and drug response. Neurology. 80: 1534-1535

    Miao S, Chen R, Ye J, Tan GH,  Li S, Zhang J, Jiang YH and Xiong ZQ. (2013) The Angelman Syndrome protein Ube3ais required for polarized dendrite morphogenesis in pyramidal neurons. J. Neurosci. 33: 327-333.

    Li HF, Ni W, Xiong ZQ, Xu J. and Wu ZY. (2013) PRRT2 c.649dupC mutation derived from de novo in paroxysmal kinesigenic dyskinesia. CNS Neurosci. Ther. 19: 61-65..

    Feng Y, Wang Y, Wang Z, Fang Z, Li F, Gao Y, Liu H, Xiao T, Li F, Zhou Y, Zhai Q, Liu X, Sun Y, Bardeesy N, Wong KK, Chen H, Xiong ZQ and Ji H.  (2012). The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss. Cancer Res. 72: 6502-6511.

    Tan GH, Liu YY, Hu XL, Yin DM, Mei L and Xiong ZQ. (2012) Neuregulin 1 represses limbic epileptogenesis through ErbB4 inparvalbumin-expressing interneurons. Nature Neuroscience. 15: 258-266.

    Guo SL, Tan GH, Li S,Cheng XW, Zhou Y, Jia YF, Xiong H, Tao J and Xiong ZQ. (2012) Serum inducible kinase is a positive regulator of cortical dendrite development and is required for BDNF-promoted dendritic arborization. Cell Research. 22: 387-398.

    Chen WJ, Lin Y, Xiong ZQ, Wei W, Ni W, Tan GH, Guo SL, He J, Chen YF, Zhang QJ, Li HF, Lin Y, Murong SX,  Xu J, Wang N, Wu ZY. (2011) Exome sequencing identifies truncating mutations in PRRT2 that casue paroxysmal kinesigenic dyskinesia. Nature Genetics. 43: 1252-1255.

    Hu XL, Chen X, Fei J and Xiong ZQ. (2011) Neuron-restrictive silencer factor is not required for the antiepileptic effect of the ketogenic diet. Epilepsia. 52:1609-1616.

    Hu XL, Chen X, Cai L, Tan GH, Xu L, Feng XY, Lu TJ, Xiong H, Fei J and Xiong ZQ. (2011) Conditional deletion of NRSF in forebrain neurons accelerates epileptogenesis in the kindling model. Cerebral Cortex.21:2158-2165.

    Chen X, Li Y, Huang Y, Feng X, Feng G, and Xiong ZQ. (2011) Pulse labeling and long-term tracing of newborn neurons in the adult subgranular zone. Cell Research. 21: 338-349.

    Sun B, Guo S, Tang Q, Li C, Zeng R, Xiong Z, Zhong C, and Ding J. (2011) Regulation of the histone acetyltransferase activity of hMOF via autoacetylation of Lys274. Cell Research. 21: 1262-1266.

    Chen Q, Zhu YC,  Yu J, Miao S, Zheng J, Xu L, Zhou Y, Li D, Zhang C, Tao J, and Xiong ZQ. (2010) CDKL5,  a  protein  associated  with  Rett syndrome, regulates neuronal morphogenesis via Rac1 signaling. J Neurosci. 30:12777-12786.

    Qiu LF, Lu TJ, Hu XL, Yi YH, Liao WP, and Xiong ZQ. (2009) Limbic epileptogenesis in a mouse model of fragile X syndrome. Cerebral Cortex. 19: 1504-1514.

    Li S, Zhang C, Takemori H, Zhou Y, and Xiong ZQ. (2009) TORC1 regulates activity-dependent CREB-target gene transcription and dendritic growth of developing cortical neurons. J. Neurosci. 29: 2334-2343.

    Chen M, Chen Q, Cheng XW, Lu TJ, Liu HX, Jia JM, Zhang C, Xu L, and Xiong ZQ (2009) Zn2+ mediates ischemia-induced impairment of the ubiquitin-proteasome system in the rat hippocampus. J. Neurochem. 111: 1094-1103.  

    Zhou Y, Lu TJ and Xiong ZQ. (2009) NGF-dependent retrograde signaling: survival versus death. Cell Research. 19: 525-526. (Preview)

    Chen M, Lu TJ, Chen XJ, Zhou Y, Chen Q, Feng XY, Xu L, Duan WH and Xiong ZQ. (2008) Differential roles of NMDA receptor subtypes in ischemic neuronal cell death and ischemic tolerance. Stroke. 39: 3042-3048.

    Jia JM, Chen Q, Zhou Y, Mao S, Zheng J, Zhang C, and Xiong ZQ. (2008) Brain-derived neurotrophic factor-tropomyosin-related kinase B signaling contributes to activity-dependent changes in synaptic proteins. J. Biol. Chem. 283: 21242-21250

    Zheng J, Shen WH, Lu TJ, Zhou Y, Chen Q, Wang Z, Xiang T, Zhu YC, Zhang C, Duan S, and Xiong ZQ. (2008) Clathrin-dependent endocytosis is required for TrkB-dependent Akt-mediated neuronal protection and dendritic growth. J. Biol. Chem. 283:13280-13288.

    Qiu HY, Guo C, Cheng XW, Huang Y, Xiong ZQ, and Ding YQ. (2008) Pitx3-CreER mice showing restricted Cre expression in developing ocular lens and skeletal muscles. Genesis. 46:324-328.

    Huang YZ, Pan E, Xiong ZQ, and McNamara JO. (2008) Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse. Neuron. 57: 546-558.

    Zhang XB, Jiang P, Gong N, Hu XL, Fei D, Xiong ZQ, Xu L, Xu TL (2008). A-type GABA receptor as a central target of TRPM8 agonist menthol. PLoS ONE, 3: e3386.

    Qiu LF, Hao YH, Li QZ, and Xiong ZQ (2008). Fragile X syndrome and epilepsy. Neurosci. Bull. 24: 338-344.

    Zhang XH, Liu F, Qian C, Zhang CL, Zhuo M, Xiong ZQ, and Li BM. (2008) Conditioning-strength dependent involvement of NMDA NR2B subtype receptor in the basolateral nucleus of amygdala in acquisition of auditory fear memory. Neuropharmacology. 55: 238-246

    Wu H, Zhou Y, and Xiong ZQ. (2007)  Transducer of regulated CREB and late phase long-term synaptic potentiation. FEBS J. 274: 3218-3223. (MiniReview)

    Chen Q, He S, Hu XL, Yu J, Zhou Y, Zheng J, Zhang S, Zhang C, Duan WH, and Xiong ZQ. (2007) Differential roles of NR2A- and NR2B-containing NMDA receptors in activity-dependent brain-derived neurotrophic factor gene regulation and limbic epileptogenesis. J. Neurosci. 27:542-552.

    Wang CL, Zhang L, Zhou Y, Zhou J, Yang XJ, Duan SM, Xiong ZQ, Ding YQ. (2007) Activity-dependent development of callosal projections in the somatosensory cortex. J. Neurosci. 27:11334-11342.

    Zhou Y, Wu H, Li S, Chen Q, Cheng XW, Zheng J, Takemori H, and Xiong ZQ. (2006). Requirement of TORC1 for late-phase long-term potentiation in the hippocampus. PLoS ONE. 1:e16.

    Wang LC, Xiong W, Zheng J, Zhou Y, Zheng H, Zhang C, Zheng LH, Zhu XL, Xiong ZQ, Wang LY, Cheng HP, and Zhou Z. (2006). The timing of endocytosis after activation of a G-protein-coupled receptor in a sensory neuron. Biophys J. 90:3590-3598.

    Xiong ZQ, Qian W, Suzuki K, and McNamara JO.  (2003).  Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration.  J. Neurosci. 23:955-960.

    Xiong ZQ and McNamara JO.  (2002).  Fleeting activation of ionotropic glutamate receptors sensitizes cortical neurons to complement attack.  Neuron 36: 363-374.

    Xiong ZQ and McNamara JO.  (2002).  Fas(t) balls and Lou Gehrig disease. A clue to selective vulnerability of motor neurons? Neuron 35: 1011-1013. (preview)

    Xiong ZQ and Stringer JL.  (2001). Prolonged bursts occur in normal calcium in hippocampal slices after raising excitability and blocking synaptic transmission. J. Neurophysiol. 86: 2625-2628.

    Xiong ZQ and Stringer JL.  (2001).  Effects of postsynaptic GABAB receptor activation on epileptiform activity in hippocampal slices. Neuropharmacology 40: 131-138.

    Xiong ZQ, Saggau P, and Stringer JL.  (2000).  Activity-dependent intracellular acidification correlates with the duration of seizure activity.  J. Neurosci. 20: 1290-1296.

    Xiong ZQ and Stringer JL.  (2000).  Extracellular pH responses in CA1 and the dentate gyrus during electrical stimulation, seizure discharges, and spreading depression.  J. Neurophysiol. 83: 3519-3524.

    Schweitzer JS, Wang H, Xiong ZQ, and Stringer JL.  (2000).  pH sensitivity of non-synaptic field bursts in the dentate gyrus. J. Neurophysiol. 84: 927-933.

    Xiong ZQ and Stringer JL.  (2000).  Sodium pump activity, not glial spatial buffering, clears potassium after epileptiform activity induced in the dentate gyrus.  J. Neurophysiol. 83: 1443-1451.

    Xiong ZQ and Stringer JL.  (2000).  Regulation of extracellular pH in the developing hippocampus.  Brain Res Dev. Brain Res. 122: 113-117.

    Xiong ZQ and Stringer JL.  (1999).  Astrocytic regulation of the recovery of extracellular potassium after seizures in vivo.  Eur. J. Neurosci. 11: 1677-1684.

    Xiong ZQ and Stringer JL.  (1999).  Cesium induces spontaneous epileptiform activity without changing extracellular potassium regulation in rat hippocampus.  J. Neurophysiol. 82: 3339-3346.

    Xiong ZQ, Cheng DH, and Tang XC.  (1998).  Effects of huperzine A on nucleus basalis magnocellularis lesion-induced spatial working memory deficit.  Acta Pharmacologica Sinica 19: 128-132.

    Xiong ZQ and Stringer JL.  (1997).  Effects of felbamate, gabapentin and lamotrigine on seizure parameters and excitability in the rat hippocampus. Epilepsy Res. 27: 187-194.

    Xiong ZQ, Yi FH, Xi CT.  (1995).  Huperzine A ameliorates the spatial working memory impairments induced by AF64A.  NeuroReport  6: 2221-2224.

    Xiong ZQ and Tang XC.  (1995).  Effect of huperzine A, a novel acetyl-cholinesterase inhibitor, on radial maze performance in rats.  Pharmacol. Biochem. Behav. 51: 415-419.

    Xiong ZQ and Tang XC, Lin JL and Zhu DY  (1995).  Effects of isovanihuperzine A on cholinesterase and scopolamine-induced memory impairment.  Acta Pharmacologica Sinica 16: 21-25.

    Xiong ZQ and Tang XC.  (1995).  Effect of –N omega-nitro-L-arginie on working memory of rats in eight-arm maze task.  Acta Pharmacologica Sinica 16: 301-304.

    实验室网址:http://www.cebsit.cas.cn/yjz/xzq_/yjfx/ 

    E-mail: xiongzhiqi@ion.ac.cn

    电话:021-54921716