陳景宗

 

陳景宗（Jin-Chung Chen）

職稱：教授

研究室名稱：神經藥理學研究室

最高學歷： Ph.D.

學校/國家：University of Illinois, USA

分機號碼：5282

電子郵件帳號：Jinchen@mail.cgu.edu.tw

個人網頁網址：http://jcc05282.wixsite.com/cgujcclab

研究室現有

博士後研究員  1 人

博士班研究生  1 人

碩士班研究生  3 人

專任研究助理  2 人

大學部專題生  10 人

研究方向及研究室特色：

神經藥理研究室主要探討多巴胺酬償系統及神經胜肽 (NPFF)在中樞神經系統上所扮演的角色，此外我們也探討若干中樞神經與精神病變議題，包括成癮與復犯機制（甲基安非他命及K他命）、精神分裂症、帕金森氏症、疼痛與憂鬱共病的中樞作用機轉。本實驗室主要的研究導向為利用藥物或基因轉殖鼠建立病變的動物模式，待病理的外顯行為確定後，再進行活體和離體的腦部神經化學、訊號傳遞與基因表現等的定性與定量分析，最後以神經藥理作驗證或以細胞培養模式探究其作用機制。在這些疾病中，我們著重於數個神經傳導系統：包括多巴胺、興奮性 (glutamate) 和抑制性(GABA)氨基酸以及HPA axis，希望經由多層次的整體性研究，確定特定神經系統在特殊病理時期的行為和生化反應，以利對疾病的瞭解或開發新型藥物。目前本實驗室發現:

（一）在藥物成癮發展過程中，前腦積核(nucleus accumbens)內的多巴胺第三亞型受體對藥物成癮具有剎車的角色，並和Cdk5-DARPP-32-PP2A這一條訊息路徑的活化有關；此外藉由場地制約行為(conditioned place preference)研究藥癮記憶消除(extinction)和復犯(relapse)則發現前腦額業的興奮性glutamate訊號對extinction具有關鍵的角色；目前我們正繼續分析中腦GABA神經元在藥癮記憶上的角色。

（二）在帕金森氏症研究上，我們發現位於側腦室的一群成體神經幹細胞(adult neural stem/progenitor cells)會受到多巴胺第三亞型受體的刺激而增生，並且能夠在小鼠模式上顯著改善因MPTP神經毒所造成帕金森氏症的動作障礙；目前，我們正在研究帕金森氏症小鼠因為長期服用L-dopa藥物所產生的異動症(dyskinesia)的神經病變機制。此外我們亦發現抑制多巴胺第三亞型受體活性，可以改善因腦部多巴胺過度活化(DAT knockout model)所造成的認知障礙。

（三）有關神經胜肽NPFF的研究，我們實驗室製造出NPFFR2 Tg mice，發現這受體過度表現會使小鼠呈現痛覺過敏(hypralgesia)和憂鬱與焦慮的行為表徵；進一步的研究顯示這基因改造鼠下視丘HPA axis過度活化導致海馬迴神經新生下降，並且醣皮質素受體的負回饋作用缺失，使動物呈現憂鬱與焦慮的狀況。此外，位於脊椎背角區的疼痛胜肽CGRP釋放量會增加，引動上行疼痛路徑在fMRI的偵測下整體活性上升，造成這基因改造鼠在各種疼痛測試中均呈現閾值下降，而產生疼痛致敏化現象。目前我們正在製備NPFFR2基因剔除鼠，並探討該受體在下視丘參與的其他生理功能。

本實驗室主要以系統學 (in vivo) 和細胞層級 (in vitro) 相輔研究，探究受體蛋白和基因在離體時的次細胞信息路徑，以及在活體上的生理與病理上的意義，以期獲致從分子-細胞-生理-行為等層次的綜觀瞭解。實驗室常使用的技術包括有：高液相層析儀(HPLC-EC/ fluorescence detection)、西方墨點法(western blot)、免疫螢光及共軛焦顯微影像分析、定量real-time PCR、磷酸酵素kinase assay、腦組織微透析(microdialysis)與局部藥物注射、細胞培養與基因植入、免疫螢光反應、動物行為分析[水平跑步、刻板行為、水迷宮學習與記憶、焦慮感測試與藥物制約行為]與一般性的生化、分生及組織切片螢光染色分析。

最近本實驗室開發先進的光遺傳學技術(optogenetics)，利用病毒AAV5所攜帶對光敏感的離子通道蛋白(ChR2或NpHR)感染具神經傳導物質專一性的Cre mice特定腦區，再利用植入的光纖維(optic fiber)激發或抑制神經活性，藉以在活體動物瞭解特定神經迴路對特定行為的影響。本實驗室每兩週舉辦一次的lab meeting，可讓實驗室的每位成員瞭解彼此所做的實驗內容和理論基礎，並可有充分溝通的機會。本實驗室與林口長庚醫院神經科學中心(NRC)有長期的合作關係探討帕金森氏症，和分析病患檢體；此外並與基隆長庚醫院合作Ketamine的成癮藥物計劃；與德國的合作團隊與國衛院則探討NPFF的中樞與週邊生理作用。

A. Publications：

1.  J.C. Chen, K.K. Rhee, D.M. Beaudry and V.D. Ramirez (1984) In vivo output of dopamine and metabolites from the rat caudate nucleus as estimated with push-pull perfusion on-line with HPLC-EC in unrestrained, conscious rats.  Neuroendocrinology 38: 362-370.

2.  V.D. Ramirez, J.C. Chen, E. Nduka, W. Lin and A.D. Ramirez (1986) Push-pull perfusion (PPP) of the hypothalumus and the caudate nucleus (CN) in conscious, unrestrained animals. Annals of the New York Academy of Sciences 473:434-448.

3.  J.C. Chen and V.D. Ramirez (1988) In vivo dopaminergic activity from nucleus accumbens, substantia nigra and ventral tegmental area in the freely moving rat: basal neurochemical output and prolactin effect. Neuroendocrinology 48:329-335

4.  J.C. Chen and V.D. Ramirez (1988) Comparison of the effect of prolactin on dopamine release from the rat dorsal and ventral striatum and from the mediobasal hypothalamus superfused in vitro. European Journal of Pharmacology 149:1-8.

5.  J.C. Chen, P.B. Crino, P.W. Schnepper and L. Volicer (1989) Increased serotonin efflux by partially oxidized serotonin. Journal of Pharmacology and Experimental Therapeutics 250:141-148.

6.  J.C. Chen and V.D. Ramirez (1989) Effects of prolactin on tyrosine hydroxylase activity of central dopaminergic neurons of male rats: a NSD 1015 study. European Journal of Pharmacology 166:473-479.

7.  P.B. Crino, B.A. Vogt, J.C. Chen and L. Volicer (1989) Neurotoxic effects of partially oxidized serotonin: tryptamine-4,5-dione. Brain Research 504:247-257.

8.  P. Cai, J.K. Snyder, J.C. Chen and L. Volicer (1989) Preparation, reactivity and neurotoxicity of tryptamine-4,5-dione. Tetrahedron Letters, 31:969-972.

9.  J. Fishman, J. Rubins, J.C. Chen and L. Volicer (1991) Selective modification of guanine nucleotide-binding proteins by tryptamine-4,5-dione, a neurotoxic derivative of 5-hydroxytryptamine (serotonin). Journal of Neurochemistry 56:1851-1854.

10. J.C. Chen, J. Tonkiss, J.R. Galler and L. Volicer (1992) Prenatal protein malnutrition enhances serotonin release from hippocampus. Journal of Nutrition 122:2138-2143.

11. J.C. Chen, A. To, P.W. Schnepper and L. Volicer (1992) Neurochemical changes, tryptophan hydroxylase activity and serotonin uptake in rat brain after intraventricular administration of tryptamine-4,5-dione. Neuropharmacology 31:215-219.

12. J.C. Chen, E. Smith and J. Fishman (1992) The opioid receptor binding of dezocine, morphine, fentanyl, butorphanol and nalbuphine. Life Sciences, 52:389-396.

13. M.S. Moolten, J.B. Fishman, J.C. Chen and K.R. Carlson (1993) Etonitazene; an opioid selective for the mu receptor types. Life Sciences, 52:199-203.

14. G.J. Blatt, J.C. Chen, D.L. Rosene, L. Volicer and J.R. Galler (1994) Prenatal protein malnutrition effects on the serotonergic system in the hippocampal formation: an immunocytochemical, ligand binding, and neurochemical study. Brain Research Bulletin 34:507-518.

15. J.C. Chen, G. Turiak, J. Galler and L. Volicer (1995) Effect of prenatal malnutrition on release of monoamines from hippocampal slices. Life Sciences, 57:1467-1475.

 16. J.C. Chen, J. Squepinilli, R. Fine and L. Volicer (1996) Neurotoxicity of free-radical mediated serotonin neurotoxin in cultured embryonic chick brain neurons. European Journal of Pharmacology, 303:109-114

17. J.C. Chen, G.Turiak, J.Galler and L.Volicer (1997) Postnatal changes of brain monoamine levels in prenatally malnorished and control rats. International Journal of Developmental Neurocsience 15: 257-263.

18. J.C. Chen, H.J. Su, L.I. Huang and M.C. Hsieh (1998) The Reductions of binding and functions of D2 dopamine receptors in the rat ventral striatum amphetamine sensitization. Life Sciences 64:343-354.

19. J.Y.Li, C.H.Wong, K.S.Huang, K.W.Liang, M.Y.Lin, P.C.Tan and J.C. Chen (1999) Morphine tolerance in arthritic rats and serotoninergic system. Life Sciences, 64:PL111-116.

20. J.C,Chen, J.-Y. Li, K.-W. Liang and Y.K. Huang (1999) Neuropeptide FF potentiates the behavioral sensitization to amphetamine and alters the levels of neurotransmitters in the median prefrontal cortex. Brain Research 816:220-224.

21. C.L.Huang, H.C.Chen, N.K.Huang, D.M.Yang, L.S.Kao, J.C. Chen, H.L.Lai and YJ Cheren (1999) Modulation of dopamine transporter activity by nicotinic acetylcholine receptors and membrane depolarization in rat phechromocytoma PC12 cells. Journal of Neurochemistry 72:2437-2444.

22. P.C. Tan, J.C. Chen, J.Y.Li, K.W.Liang, C.H.Wong and Eagle Y.K.Huang (1999) Modulation of naloxone-precipitated morphine withdrawal syndromes in rats by neuropeptide FF analogues. Peptides, 20:1211-1217.

23. E.Y.-K. Huang, J.Y. Li, P.P.-C. Tan, C.H. Wong and J.C. Chen (2000) The cardiovascular effects of PFRPamide and PRF(Tic)amide, a possible agonist and antagonist of neuropeptide FF (NPFF). Peptides, 21:205-210.

24. J.C. Chen, K.W. Liang, C.S. Liang and Y.C. Chiang (2001) Significance of glutamate and dopamine neurons in the ventral pallidum during the expression of behavioral sensitization to amphetamine. Life Sciences, 68 (9): 973-983.

25. J.C. Chen, K.W. Liang and Eagle Y.K. Huang (2001) Differential effects of endomorphine-1 and -2 on amphetamine sensitization: neurochemical and behavioral aspects. Synapse, 39 (3): 239-248.

26. J.C. Chen, C.H. Wong, Y.K. Huang, T.C. Tang and J.Y. Li (2001) Modulations of spinal serotonin activity affect the development of morphine tolerance. Anesthesia and Analgesia 92(6):1563-1568.

27. Y.K. Huang, J.Y. Li, C.H. Wong, P.C. Tan and J.C. Chen (2002) Dansyl- PQRamide, a neuropeptide FF receptor analog, induces conditioned place preference. Peptides, 23 (3):489-496.

28. G.C. Yeh, J.C. Chen, H.C. Tsai, H.H. Wu, C.Y. Lin, P.C. Hsu and Y.C. Peng (2002) Amphetamine inhibits the N-methyl-D-aspartate receptor-mediated responses by directly interacting with the receptor/channel complex. Journal of Pharmacology and Experimental Therapeutics 300(3):1008-1016.

29. J.J. Hwang, M.H. Liao, T.C. Yen, S.P. Wey, K.J. Lin, W.H.T. Pan, J.C. Chen and G. Ting (2002) Biodistribution study of [99mTc]TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography. Applied Radiation and Isotopes, 57:35-42.

30. H.C. Hsieh, H.Y. Li, M.Y. Lin, Y.F. Chiou, S.Y. Lin, C.H. Wong and J.C. Chen (2002) Spatial and temporal profile of haloperidol-induced immediate early gene expression and phosphoCREB binding in the dorsal and ventral striatum of amphetamine- sensitized rats. Synapse, 45:230-244.

31. J.C. Chen, P.C. Chen and Y.C. Chiang (2003) D3 dopamine receptors are down-regulated in amphetamine-sensitized rats and their putative antagonists modulate the locomotor sensitization to amphetamine. Brain Research, 972(1-2):159-167.

32. Eagle Y.K. Huang, P.L. Tao, J.Y. Li, C.H. Wong and J.C. Chen (2003) Endomorphin-1 and -2 induce naloxone-precipitated withdrawal syndromes in rats. Peptides, 24:477-481.

33. K.J. Lin, T.C. Yen, S.P. Wey, J.J. Hwang, X.X. Ye, K.Y. Tzen, Y.K. Fu and J.C. Chen (2004) Characterization of the binding sites for 123I-ADAM and the relationship to the serotonin transporter in rat and mouse brains using quantitative autoradiography. Journal of Nuclear Medicine, 45:673-681.

34. P.C. Chen and J.C. Chen (2005) Enhanced Cdk5 activity and p35 translocation in the ventral striatum of acute and chronic methamphetamine-treated rats. Neuropsychopharmacology, 30:538-549.

35. J.-S. Wang, Y.S. Li, J.C. Chen, and Y.W. Chen (2005) Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arteriosclerosis, Thrombosis and Vascular Biology, 25:454-460.

36. T.-H. Yeh, H.M. Hwang, J.C. Chen, Tony Wu, A.H. Li and H.L. Wang (2005) Glutamate transporter function of rat hippocampal astrocytes is impaired following the global ischemia. Neurobiology of Disease, 18:476-483.

37. J.C. Chen, H.C. Hong, J.L. Lu, Y.C. Chiang, H.M. Huang, H.L. Wang, Tony Wu, J.J. Liao and T.S. Yeh (2005) Down-regulation of the glial glutamate transporter GLT-1 in rat hippocampus and striatum and its modulation by a group III metabotropic glutamate receptor antagonist following transient global forebrain ischemia. Neuropharmacology, 49:703-714.

38. Eagle Y.K. Huang, W.Z. Li and J.C.Chen (2006) Rat NPFF1 receptor-mediated signaling: functional comparison of neuropeptide FF (NPFF), FMRFamide and PFR(Tic)amide. Peptides, 27:1005-1014.

39. P.C. Chen, C.L. Lao and J.C. Chen (2007) Dual alteration of limbic dopamine D1 receptor-mediated signaling and Akt/GSK3 pathway in dopamine D3 receptor mutants during the development of methamphetamine sensitization. Journal of Neurochemistry 100:225-241.

40. C.H. Huang, J.C. Cheny, J.C. Chen* and C.P. Tseng* (2007) Evaluation of the role of Disabled-2 in nerve growth factor-mediated neurite outgrowth and cellular signaling, Cellular Signaling, 19:1339-1347. (*corresponding)

41. Y.C. Chiang and J.C. Chen (2007) The role of the cannabinoid type 1 receptor and down-stream cAMP/DARPP-32 signal in the nucleus accumbens of methamphetamine-sensitized rats, Journal of Neurochemistry, 103:2505-2517.

42. P.Y. Chang, C.H. Chuang, J.C. Chen and C.-S. Tung (2008) Behavioral and pharmacological effects of amperozide and serotonin agents on nigrostriatal and mesolimbic dopamine systems, J. Chinese Physiology, 51(2):106-115.

43. H.L. Liu, Y.Y. Wai, W.S. Chen, J.C. Chen, P.H. Hsu, X.Y. Wu, W.C. Huang, T.C. Yen and J.J. Wang (2008) Hemorrhage detection during focused-ultrasound induced blood–brain-barrier opening by using susceptibility-weighted magnetic resonance imaging, Ultrasound in Medicine & Biology, 34(4):598-606.

44. H-L Liu, P-H Hsu, P-C Chu, Y-Y Wai, J.C. Chen, C-R Shen, T-C Yen and J-J Wang (2009) Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles: usefulness for distinguishing between focused ultrasound-induced blood-brain barrier disruption and brain hemorrhage. Journal of Magnetic Resonance Imaging 29:31-38.

45. J.C. Chen, P.C. Chen and Y.C. Chiang (2009) Molecular mechanism of psychostimulant addiction. Chang-Gung Medical Journal, 32:148-154.

46. P.C. Chen, C.L. Lao and J.C. Chen (2009) The D3 dopamine receptor inhibits dopamine release in PC-12/hD3 cells by autoreceptor signaling via PP-2B, CK-1 and Cdk-5, Journal of Neurochemistry, 110:1180-1190.

47. K.J. Lin, H.L. Liu, P.H. Hsu, Y.H. Chung, W.C. Huang, J.C. Chen, S.P. Wey, T.C. Yen and I.T. Hsiao (2009) Quantitative microSPECT/CT for detecting focused ultrasound induced blood-brain barrier opening in the rat, Nuclear Medicine and Biology, 36:853-861.

48. H-L Liu, Y-Y Wai, P-H Hsu, L-A Lyu, J-S Wu, C-R Shen, J-C Chen, T-C Yen and J-J Wang (2010) In vivo assessment of macrophage CNS infiltration during disruption of the blood–brain barrier with bocused ultrasound: a magnetic resonance imaging study, Journal of Cerebral Blood Flow & Metabolism, 30:177-186.

49. C.H. Hsieh, H.Y. Li and J.C. Chen (2010) Nitric oxide and interleukin-1b mediate noradrenergic induced corticotrophin-releasing hormone release in organotypic cultures of rat paraventricular nucleus, Neuroscience, 165:1191-1202.

50. F. Kersanté, J.-Y. Wang, J.-C. Chen, C. Mollereau and Jean-Marie Zajac (2011) Anti-opioid
 effects of neuropeptide FF receptors in the ventral tegmental area, Neuroscience Letters, 
488: 305-309.
51. Y.-L. Shen, J.-C. Chen and R.-M. Liao (2011) Place conditioning and neurochemical responses
 elicited by the aftereffect of acute stressor exposure to an elevated stand, Neuroscience Letters, 
504:156-159.

52. Y.T. Lin and J.C. Chen (2011) The involvement of dorsal root ganglia BDNF-TrkB in inflammatory pain in vivo and in vitro, Journal of Neuroinflammation, 8:126-147.

53. D.-J. Kao, Allen H Li, J.C. Chen, R.S. Luo, Y.L. Chen, J.C. Lu and H.L. Wang (2012) CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Nav1.8 sodium channels in dorsal root ganglion neurons, Journal of Neuroinflammation, 9:189.

54. P.K. Chao, K.T. Lu, Y.L. Lee, J.C. Chen, H.L. Wang, Y.L. Yang, M.Y. Cheng, M.F. Liao, L.S. Ro (2012) Early systemic granulocyte-colony stimulating factor treatment attenuates neuropathic pain after peripheral nerve injury, PLoS ONE, 8:1-13.

55. H.T. Chen, N.Y. Ruan, J.C. Chen* and Z.Y. Lin* (2012), Dopamine D2 receptor-mediated Akt/GSK3b signaling: Initiation by D2S receptor and role in quinpirole-induced behavioral activation, ASN NEURO, 4(6). (*, co-coresponding)

56. C.C. Lin, H.L. Hsieh, R.H. Shih, P.L. Chi, S.E. Cheng, J.C. Chen* and C.M. Yang* (2012) NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin- induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes, Cell Communication and Signaling, 10:35. (*, co-coresponding)

57. L.H. Chow, P.L. Tao, J.C. Chen, R.M. Liao, E.P. Chang and E.Y.K. Huang (2013) A possible correlation between oxytocin-induced and angiotensin IV-induced anti-hyperalgesia at the spinal level in rats. Peptides, 39:21-28.

58. T.C. Wu, H.T. Chen, H.Y. Chang, C.Y. Yang, M.C. Hsiao, M.-L. Cheng and J.-C. Chen (2013) Mineralocorticoid receptor antagonist prevents chronic corticosterone induced depression-like behaviors, Psychoneuroendocrinology, 38:871-883.

59. C.L. Lao, C.S. Lu and J.C. Chen (2013) Dopamine D3 receptor activation promotes neural stem / progenitor cell proliferation through AKT and ERK1/2 pathways and expands type-B and type–C cells in adult subventricular zone, Glia, 61:475–489.

60. P-H Hsu, K-C Wei, C-Y Huang, C-J Wen, T-C Yen, C-L Liu, Y-T Lin, J-C Chen, C-R Shen*, and H-L Liu* (2013) Noninvasive and targeted gene delivery into the brain using microbubble-facilitated focused ultrasound, PLoS ONE, 8(2): e57682.

61. C.L. Lao, Y.H. Kuo, Y.T. Hsieh and J.C.Chen (2013), Intranasal and subcutaneous administration of dopamine D3 receptor agonists functionally restores nigrostriatal dopamine in MPTP-treated mice, Neurotoxicity Research, 61:475-489.

62. Y.C. Chiang, Y.N. Lo and J.C. Chen (2013) Dopamine D2 receptors crosstalk with cannabinoid CB1 receptors at ERK1/2 signal and regulate Cnr1 promoter activity, Journal of Neurochemistry, 127:163-176.

63. H.T. Chen and J.C. Chen (2014) Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity, Learning and Memory, 22:149-158.

64. S.C. Kao, Y.T. Lin, Y.J. Dey and J.C. Chen (2015) The effects of Neuropeptide FF receptor subtype 2 over-expression on nociception and morphine tolerance, European Journal of Pain, 20:895-906.

65. Y.T. Lin, T.Y. Liu, C.Y. Yang, Y.L. Yu, T.C. Chen, Y.J. Day, C.C. Chang, G.J. Huang and J.C. Chen (2016) NPFFR2 stimulates stress-related depressive behaviors through HPA axis modulation, Psychoneuroendocrinology, 71:73-85.

66. W.Y. Tzeng, H.H. Wu, C.Y. Wang, J.C. Chen, L. Yu and C.F. Cherng (2017) Sex differences in stress and group housing effects on the number of newly proliferated cells and neuroblasts in middle-aged dentate gyrus. Frontiers in Behavioral Neuroscience, 10, 249. 

Books and Chapters：

1.J.C. Chen, A. Ramirez and V.D. Ramirez (1985) Prolactin effect on in vivo striatal

    dopaminergic activity as estimated with push-pull perfusion in male rat. In:

    Prolactin, Basic and Clinical Correlates,  R.M.  Macleod et al., eds., Liviana press,

    pp.523-532.

2. L. Volicer, J.C. Chen, P.B. Crino, B.A. Vogt, J. Fishman, J. Rubins, P.W. Schnepper

    and N. Wolfe (1989) Neurotoxic properties of a serotonin oxidation product: possible

    role in Alzheimer's disease. In: Progress in Clinical and Biological Research Vol.

    317: Alzheimer's Disease and Related Disorders, Alan R. Liss, Inc., NY, pp. 453-465.

3. 藥理學  1999年 楊春茂 林麗慧 陳景宗 余淑美 林光輝 郭詩憲合著 匯華圖書出版有限公

  司 (ISBN 957-594-026-1 C5430)

4. 掌握優勢的關鍵 腦科學知識  2004年 曾志朗 洪蘭 賴其萬 胡海國 白明奇 朱迺欣 謝仁俊

   陳景宗合著 東元科技文教基金會 (ISBN：9789570829020)

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