呂俊宏教授首頁

June-Horng Lue

Medical College of National Taiwan University

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個人經歷

個人專長

研究領域

研究成果

個人興趣

上課講義

　

連絡資訊

地址: 台北市仁愛路一段一號六樓

電話: 23123456-88178

傳真: 2395-5804

e-mail: thomas@ntu.edu.tw

　

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個人經歷

學歷: 國立台灣大學醫學院解剖所博士

現職: 國立台灣大學醫學院解剖學暨細胞生物學研究所教授

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獲獎

      2001 臺灣大學 教學優良獎

2001 臺灣大學醫學院北美校友基金會 最佳基礎教學獎

2002 臺灣大學 教學傑出獎

2007 臺灣大學 教學優良獎

2008 臺灣大學 教學優良獎

2009 臺灣大學 教學優良獎

2011 臺灣大學 教學優良獎

2012 臺灣大學 教學優良獎

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個人專長

細胞免疫化學

神經追蹤技術

電子顯微鏡技術

　

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研究領域與重點

    最近幾年主要的研究方向以正中神經損傷模式為基礎，探討相對應的頸背根神經節及楔狀神經核生化因子的變動，藉以瞭解楔狀神經核在原本為接收來自上肢、軀幹及頸部背根神經節經由Aa/b初級傳入神經纖維所傳遞有關觸覺、震動覺、兩點間辨識覺及本體感覺等訊息，它如何因應轉變而與傷害性訊息傳遞有所關聯。期望藉由這些基礎研究，有助於臨床上周邊神經病變疼痛機轉的探討。在過去數年間，我們研究具體而重要成果敘述如下:

1. 確立正中神經截斷損傷後在背根神經節NPY的表現時程及其在楔狀神經核的可能來源：以螢光追蹤劑注
  射於正中神經，確認它主要分怖位置為C6及C7背根神經節。當正中神經截斷損傷後，在背根神經節中
  NPY免疫表現的神經元數量會隨損傷時期增長而變高，並且在第四週達到最大量。仔細地探討變化時程
  發現NPY表現神經元的數量變化與在楔狀神經核的時程相吻合，另外利用神經追蹤劑標誌法加以證實僅
  只有受傷的神經元會被誘發產生NPY，再透過初級傳入神經投射至同側楔狀神經核；然而當正中損傷前
  施以背根神經截斷手術時，在同側楔狀神經核則無法偵測到任何的NPY神經纖維。綜合以上得知，楔狀
  神經核的NPY神經纖維來源，唯一來自背根神經節中的受傷神經元的初級傳入神經纖維，它可能影響楔
  狀丘腦接轉神經元，因而將神經病變疼痛訊息向上傳遞至丘腦 (Tsai et al., 2007. J. Neurotrauma)。

2. 證明正中神經截斷損傷後楔狀神經核中的NPY神經終末與楔狀丘腦接轉神經元的關係：正中神經截斷損
  傷後四週，動物犧牲前三天在對側丘腦注射山葵過氧化氫酵素標誌楔狀丘腦接轉神經元，結果發現NPY
  神經終末與楔狀丘腦接轉神經元的樹突直接形成軸－樹突觸，由此可見神經損傷時誘發NPY產生，當它
  受刺激而釋放可能調高楔狀丘腦接轉神經元的神經活性，進而參與神經病變疼痛訊息的傳遞
    (Yeh et al., 2008. J. Chemical Neuroanatomy)。

3. 探討正中神經損傷誘導NPY產生的作用：先前的結果已知正中神經截斷損傷後四週，在頸背根神經節及
  楔狀神經核NPY免疫標誌數量達到最高點；令人意外的是損傷的正中神經以低電流強度刺激時楔狀神經
  核NPY免疫標誌數量比高電流強度刺激時來得顯著地少，而未經電刺激則楔狀神經核NPY免疫標誌數量
  為最高；同時低電流強度刺激處理的楔狀神經核中的c-Fos免疫標誌神經元數量顯著高於高電流強度刺激
  處理組，但在未經電刺激組則幾乎無任何c-Fos免疫標誌神經元被偵測到。因此推測高電流強度刺激時
     NPY釋放量小，使得楔狀神經核中的c-Fos免疫標誌神經元數量少；相對地，以低電流強度刺激而NPY
  釋放量大，使得楔狀神經核中的c-Fos免疫標誌神經元數量多。隨後以NPY受體的拮抗劑處理，發現它會
  使得楔狀神經核中的c-Fos免疫標誌神經元數量明顯地減少，以此證實NPY與c-Fos誘發的關係。當檢視
  它們與正中神經病變疼痛的相關性時，以NPY或NPY受體的拮抗劑處理，發現它們會分別使得正中神經
  慢性纏繞損傷動物的觸覺痛有加劇或舒緩，伴隨其c-Fos免疫標誌神經元在楔狀神經核中的表現量有增多
  或變少的情形。由此可推測神經損傷後誘發NPY的產生，當低電流強度刺激使得大直徑神經纖維及其終
  末的NPY釋放，使得楔狀丘腦接轉神經元的神經活性增高而誘導產生c-Fos。由於發現楔狀神經核中的
     c-Fos免疫標誌神經元數量多時，正中神經損傷動物的觸覺痛程度嚴重而明顯；反之，楔狀神經核中的
     c-Fos免疫標誌神經元數量少時，則神經損傷動物的觸覺痛程度輕微而弱，因此楔狀神經核中c-Fos免疫
  標誌數量似乎可以作為參與傳遞觸覺痛的指標。由以上的結果得知NPY因神經損傷而新合成產生，當受
  外界刺激時NPY會因此而被釋放至楔狀神經核中誘發c-Fos的產生，進而可能與正中神經病變觸覺痛的
  訊息傳遞有所關聯 (Tsai et al., 2009. J. Neurotrauma)。

4. 術前以局部麻醉劑處理，可以抑制正中神經損傷後的異位性放電，並有效地避免背根神經節及楔狀神經
  核NPY大量的產生，進而降低電刺激後楔狀神經核中的c-Fos免疫標誌神經元數量，因而可能可以防治或
  減緩神經病變疼痛的程度 (Lin et al., 2009. J. Chemical Neuroanatomy)。

5.以streptozotocin誘發糖尿病並配合正中神經損傷手術，結果發現NPY在背根神經節及楔狀神經核的表現
  時程提早，在神經損傷後兩週即達到最大量；同時發現糖尿病實驗動物背根神經節中NT-3免疫標誌神經
  元數量在神經損傷後兩週即下降到最低點，比非糖尿病動物在神經損傷後四週才達到最低點，其時程有
  顯著地提早，由此間接證實背根神經節中大型神經元NT-3的下降可能為誘發NPY的產生，因此避免NT-3
  的下降或其數量的補充，或許可以作為將來防治或減緩神經病變疼痛的處置方式之一
    (Lin et al., 2010. J. Chemical Neuroanatomy)。

            6. 另外與耳鼻喉科楊怡和教授的合作成果主要以aminoglycoside類抗生素在中耳鼓膜上給藥，探討其對與
        平衡有關的半規管、球囊及橢圓囊等毛細胞的影響及其前庭肌電位變化時，結果證實施以aminoglycoside
                 等藥物會造成半規管及球囊的第一型毛細胞退化並引起前庭肌電位的改變 (Day et al. 2007. Ear & Hearing
                 ；論文編號12)。甚至於球囊的第一型毛細胞會因自我凋亡而造成數量下降而顯著地低於控制組，因而使
        得其前庭肌電位低於控制組，由此推論前庭肌電位與第一型毛細胞活性有相當高的密切關係 (Lue et al.,
                2009. Audiology and Neurotolgy；論文編號08)；另外可能原因是aminoglycoside處理使得前庭神經節的
        鈉離子通道Nav1.8免疫標誌神經元數量下降 (Cheng et al., 2010. NeuroToxicology；論文編號05)或NPY
        免疫標誌神經元數量下降及SP免疫標誌神經元數量上升所導致
                (Lin et al., 2010. J. Chemical Neuroanatomy)。

 

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研究成果

  1. Wang TJ, Lue JH, Shieh JY & Wen CY (1996) Localization and morphometry of the somatostatin-immunoreactive neurons in the rat cuneate nucleus. Australian & New Zealand Journal of Medicine 26: 481. (SCI) 計畫編號: NSC-86-2314-B-002-142


  2. Lue JH, Shieh JY & Wen CY (1996) The synaptic relationships between glycine-immunoreactive terminals, primary afferent terminals and cuneothalamic relay neurons in the rat cuneate nucleus. Australian & New Zealand Journal of Medicine 26: 462. (SCI) 計畫編號: NSC-85-2331-B-002-237


  3. Lue JH, Jiang-Shieh YF, Shieh JY & Wen CY (1996) The synaptic interrelationships between primary afferent terminals, cuneothalamic relay neurons and GABA-immunoreactive terminals in the rat cuneate nucleus. Neuroscience Research 24: 363-371. (SCI) 計畫編號: NSC-79-0412-B-002-141


  4. Cheng HT, Chang H, Lue JH, & Wen CY (1996) Unpredictability of triphenyltetrazolium chloride in staining irreversible ishchaemia-reperfusion injury in the skeletal muscle of rats. Europen Journal of Surgery 162:407-412. (SCI)


  5. Lue JH, Jiang-Shieh YF, Shieh JY, Ling EA & Wen CY (1997) Multiple inputs of GABA-immunoreactive neurons in the cuneate nucleus of the rat. Neuroscience Research 27: 123-132. (SCI) 計畫編號: NSC-80-0412-B-002-157


  6. Lue JH, Shieh WF, Chen SH, Shieh JY & Wen CY (1997) Morphometric study of glycine-immunoreactive neurons and terminals in the rat cuneate nucleus. Journal of Anatomy 191: 375-385. (SCI) 計畫編號: NSC-83-0412-B-0002-048


  7. Lue JH, Lai SM, Wang TJ, Shieh JY & Wen CY (1997) Synaptic relationshipsbetween corticocuneate terminals and glycine-immunoreactive neurons in the rat cuneate nucleus. Brain Research 771: 167-171. (SCI) 計畫編號: NSC-86-2314-B-0002-157


  8. Shieh JY, Chang HM, Lue JH & Wen CY (1998) Effect of axotomy along with hypoxia on the NADPH-D activity in the brainstem motor neurons of albino rats. Faseb Journal 12:A946. (SCI) 計畫編號: NSC-87-2314-B-002-217


  9. Shieh JY, Chang HM, Lue JH & Wen CY (1999) Ultrastructural study of the NADPH-D expression in the superior cervical ganglion of the hamster.. Faseb Journal 13:A344. (SCI) 計畫編號: NSC-87-2314-B-002-217


  10. Lue JH, Shieh JY, Wen CY & Chen SH (2000) Cuneothalamic relay neurons are postsynaptic to intrinsic glycine-immunoreactive terminals in the rat cuneate nucleus. Synapse 37:222-231. (SCI) 計畫編號: NSC-85-2331-B-0002-237


  11. Tseng CY, Lue JH, Chang HM, Wen CY & Shieh JY (2000) Ultrastructural localization of NADPH-d/n-NOS expression in the suprerior cervical ganglion of the hamster. Journal of Anatomy 197:461-475. (SCI) 計畫編號: NSC-88-2314-B-002-056


  12. Wang TJ, Lue JH, Shieh JY & Wen CY (2000) Somatostatin-IR neurons are a major subpopulation of the cuneothalamic neurons in the rat cuneate nucleus. Neuroscience Research 38:199-207. (SCI)計畫編號: NSC-86-2314-B-002-142


  13. Chang HM, Ling EA, Lue JH, Wen CY & Shieh JY. (2000) Melatonin attenuates neuronal NADPH-d/NOS expression in hypoglossal neucleus of adult rat following peripheral nerve injury. Brain Research 873:243-251. (SCI) 計畫編號: NSC-88-2314-B-002-056


  14. Lue JH, Chen SH Shieh JY & Wen CY (2001) Afferent synaptic contacts on glycine-immunoreactive neurons in the rat cuneate nucleus. Synapse 41:139-149. (SCI) 計畫編號: NSC-86-2314-B-002-157


  15. Tseng CY, Lue JH, Wen CY & Shieh JY (2001) Ultrastructural identification of sympathetic component in the hypoglossal nerve of hamsters using degeneration and HRP methods. Journal of Anatomy (revised) (SCI) 計畫編號: NSC-88-2314-B-002-056


  16.  Tseng CY, Lue JH, Lee SH, Wen CY & Shieh JY (2001) Evidence of neuroanatomical connection between superior cervical ganglion and hypoglossal nerve in the hamster as revealed by tract-tracing and degeneration methods. Journal of Anatomy 198:407-421. (SCI) 計畫編號: NSC-88-2314-B-002-056


  17. Day AS, Lue JH, Shieh JY & Wen CY (2001) Aβ-fiber intensity stimulation of chronically constricted median nerve induces c-fos expression in thalamic projection neurons of the cuneate nucleus in rat with behavioral signs of neuropathic pain. Brain Research 895:194-203. (SCI)計畫編號: NSC-88-2314-B-002-080 and NSC-89-2314-B-002-132


  18. Chang HM, Lue JH, Wen CY & Shieh JY. (2001) Axotomy along with hypoxia enhances the neuronal NADPH-d/NOS expression in lower brainstem motor neurons of adult rat. Experimental Neurology. Experimental neurology 171:116-126.


  19. Day AS. Wen CY. Shieh JY. Sun WZ. Lue JH. (2001) Somatic noxious mechanical stimulation induces Fos expression in the postsynaptic dorsal column neurons in laminae III and IV of the rat spinal dorsal horn. Neuroscience Research - Supplement  40(4):343-50.


  20. Wang TJ. Lue JH. Shieh JY. Wen CY. (2001) The distribution and characterization of NADPH-d/NOS-IR neurons in the rat cuneate nucleus. Brain Research 910(1-2):38-48.


  21. Tsyr-Jiuan Wang , June-Horng Lue , Ching-Hsiang Wu , Jeng-Yung Shieh , Chen-Yuan Wen.(2002) Neurogenesis of cuneothalamic neurons and NO- containing neurons in the cuneate nucleus of the rat. Experimental Brain Research 142:327-334.


  22. Chang HM, Ling EA, Chen CF, Lue JH, Wen CY and Shieg JY. (2002) Melatonin attenuates the neuronal NADPH-d/NOS expression. In the nodose ganglion of acute hypoxic rats. J Pineal Res. 32: 1-9


  23. Chang HM, Liao WC, Lue JH. Wen CY, Shieh JY. (2003) Up regulation of NMDA receptor and neuronal NADPH-d/NOS expression in the nodose ganglion of acute hypoxic rats. J Chem Neuroanat. 25(2):137-47.


  24. Tsai YJ, Leong SM, Day AS, Wen CY, Shieh JY, Lue JH. (2004 )A time course analysis of the changes in neuropeptide Y immunoreactivity in the rat cuneate nucleus following median nerve transection. Neurosci Res. 48(4):369-77


  25. Chang HM, Wei IH, Tseng CY, Lue JH, Wen CY, Shieh JY. (2004)Differential expression of calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT) in the axotomized motoneurons of normoxic and hypoxic rats. J Chem Neuroanat. 28(4):239-51.


  26. Chang HM, Tseng CY, Wei IH, Lue JH, Wen CY, Shieh JY. (2005 ) Melatonin restores the cytochrome oxidase reactivity in the nodose ganglia of acute hypoxic rats. J Pineal Res. 39(2):206-14.


  27. Tseng CY, Wei IH, Chang HM, Lue JH, Wen CY, Shieh JY.(2005) Ultrastructural identification of a sympathetic component in the hypoglossal nerve of hamsters using experimental degeneration and horseradish peroxidase methods. Cells Tissues Organs 180(2):117-25.


  28. Day AS, Lue JH, Yang TH & Young YH. (2007) Effect of intratympanic application of aminoglycosides on click-evoked myogenic potentials in Guinea pigs. Ear Hear 28:18-25.


  29. Tsai YJ, Lin CT, Lue JH. (2007) Characterization of the induced neuropeptide Y-like immunoreactivity in primary sensory neurons following complete median nerve transection. J Neurotrauma. 24:1878-1888.


  30. Yeh JH, Lue JH, Wang HY, Huang CT & Tsai YJ. (2008) Synaptic relationships between induced neuropeptide Y-like immunoreactive terminals and cuneothalamic projection neurons in the rat cuneate nucleus following median nerve transection. J Chem Neuroanat. 36:27-32.


  31. Hsu WC, Wang JD, Lue JH, Day AS & Young YH. (2008) Physiological and morphological assessment of the saccule in Guinea pigs after noise exposure. Arch Otolaryngol Head Neck Surg. 134:1099-1106.


  32. Lue JH, Day AS, Cheng PW & Young YH. (2009) Vestibular evoked myogenic potentials are heavily dependent on type I hair cell activity of the saccular macula in guinea pigs. Audiol Neurootol.14:59-66.


  33. Tsai YJ, Lin CT, Huang CT, Wang HY, Tien LT, Chen SH & Lue JH. (2009) Neuropeptide Y modulates c-Fos protein expression in the cuneate nucleus and contributes to mechanical hypersensitivity following rat median nerve injury. J Neurotrauma. 26:1609-1621.


  34. Lin CT, Wang HY, Tsai YJ, Huang CT, Chen SH & Lue JH. (2009) Pre-treatment with lidocaine suppresses ectopic discharges and attenuates neuropeptide Y and c-Fos expressions in the rat cuneate nucleus following median nerve transection. J Chem Neuroanat. 38:47-56.


  35. Hsieh YL, Lin WM, Lue JH, Chang MF & Hsieh ST. (2009) Effects of 4-methylcatechol on skin reinnervation: promotion of cutaneous nerve regeneration after crush injury. J Neuropathol Exp Neurol. 68:1269-1281.


  36. Cheng PW, Lue JH, Lin CT, Day AS, Young YH. (2010) Assessment of gentamicin-induced vestibulotoxicity by click and galvanic vestibular-evoked myogenic potentials: a guinea pig investigation. Neurotoxicology 31:121-125.

  37. Chen JJ, Lue JH, Lin LH, Huang CT, Chiang RP, Chen CL, Tsai YJ. (2010) Effects of pre-emptive drug treatment on astrocyte activation in the cuneate nucleus following rat median nerve injury. Pain 148:158-166.

  38. Lin CT, Tsai YJ, Chen SH, Wang HY, Lin LH,Lue JH. (2010) Early expression of injury-induced neuropeptide Y in primary sensory neurons and the cuneate nucleus in diabetic rats with median nerve transection. J Chem Neuroanat 40:102-111.

  39. Lin CT, Young YH, Cheng PW, Lue JH. (2010) Effects of gentamicin on guinea pig vestibular ganglion function and on substance P and neuropeptide Y. J Chem Neuroanat 40:286-292.

  40. Luo KR, Chao CC, Hsieh PC,Lue JH, Hsieh ST: Effect of glycemic control on sudomotor denervation in type 2 diabetes. Diabetes Care 2012. FEB; 35: 612-616. (Co-corresponding author)

  41. Wang SH, Liang CJ, Wu JC, Huang JJ, Chien HF, Tsai JS, Yen YS, Tseng YC, Lue JH, Chen YL: Pigment epithelium-derived factor reduces the PDGF-induced migration and proliferation of human aortic smooth muscle cells through PPARg activation. The International Journal of Biochemistry & Cell Biology. 2012. FEB; 44:280-289. (Co-corresponding author)

  42. Wang HY, Tsai YJ, Chen SH, Lin CT, Lue JH: Nitric oxide implicates c-Fos expression in the cuneate nucleus following electrical stimulation of the transected median nerve. Neurochemical Research 2012. JAN: 37:84-95. (Corresponding author)

  43. Chen SH, Tsai YJ, Wang HY, Lin CT, Li SF,Lue JH: Decreases of glycine receptor expression induced by median nerve injury in the rat cuneate nucleus contributes to NPY release and c-Fos expression. Life Sciences 2012. FEB; 90:278-288. (Corresponding author)

  44. Chen SH, Tsai YJ, Lin CT, Wang HY, Li SF, Lue JH: Changes in GABA and GABAB receptor expressions are involved in neuropathy in the rat cuneate nucleus following median nerve transection. Synapse 2012. 66:561-572 (Corresponding author)

  45. Hsieh YL, Chiang H, Lue JH, Hsieh ST: P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy. Experimental Neurology 2012. 235:316-325 (Co-corresponding author)

  46. Lin CT, Tsai YJ, Wang HY, Chen SH, Lin TY ,Lue JH  Preemptive treatment of lidocaine attenuates neuropathic pain and reduces pain-related biochemical markers in the rat cuneate nucleus in median nerve chronic constriction injury model. Anesthesiology Research and Practice 2012 (doi:10.1155/2012/921405) (Corresponding author)

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桌球 賞鳥 昆蟲採集 游泳

 

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最後修改日期：2/15/2011