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梁淑鈴

老師姓名:梁淑鈴

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職稱:助理教授

研究室星型膠細胞及神經突觸訊息生理研究室

最高學歷博士

學校/國家國立陽明大學生理學研究所/台灣

分機號碼3688

電子郵件帳號 slliang@mail.cgu.edu.tw

個人網頁網址

研究室現況:

博士後研究員 人

博士班研究生 人

碩士班研究生1 人

專任研究助理 2人

大學部專題生 人

工讀生1人

研究方向及研究室特色:

研究方向:

   膠細胞及神經突觸訊息生理研究室是國內目前少數研究腦神經細胞與星型膠細胞突觸傳導及可塑性的實驗室之ㄧ,結合電生理學、藥理學、腦中酵素或蛋白質的定量及定性分析及動物生殖行為觀察實驗,本實驗室有四大研究方向。

  • 探討醯胺酸-麩胺酸循環參與調控新生鼠的女性化的麩胺酸及丙胺基丁酸突觸效能的細胞機制。
  • 多巴胺第二型受體與醯胺酸-麩胺酸循環交互作用調控性別分化的分子細胞機制。
  • 古柯鹼及安非他命調節轉錄胜肽CART對投射到胃腸的迷走神經運動背核神經元的放電活性及突觸訊息輸入的調控。
  • 研究醯胺酸-麩胺酸循環參與調控顳葉癲癇鼠的海馬迴CA1神經元的丙胺基丁酸突觸效能的細胞機制。

研究主題背景簡介:

一直以來,分佈於中樞神經系統內的膠細胞(glial cell)[包括星膠細胞(astrocytes)及寡突膠細胞(oligodendrocytes)],被認為只是附著在神經細胞上的輔助細胞 [“Glia”這個字源自希臘字的”gliok”,意思是黏膠 (glue)]。最近十幾年來的研究則發現,膠細胞的細胞膜具有各種神經傳遞物質的受體、離子孔道及轉運蛋白,當膠細胞膜上的受體結合上配合基(ligand)後,膠細胞能被活化,接著產生能沿著膠細胞之間傳播的鈣離子波(calcium wave)300—400微米遠。膠細胞也能分泌膠細胞傳遞物質(gliotransmitters),其中包括有麩胺(glutamate; Glu)及腺嘌呤核苷三磷酸(ATP)等,進一步研究則發現膠細胞與其附著的神經細胞類似,具有促進突觸生成作用(synaptogenesis),調控神經可塑性(neuronal plasticity)及神經突觸傳遞(synaptic transmission)等功能,其中位於神經細胞與星膠細胞之間的胺酸麩胺酸循環(glutamine -glutamate cycle; GGC)則是在調控麩胺(glutamatergic)及丙基丁酸(GABAergic)神經元的神經突觸可塑性(synaptic plasticity),扮演重要角色。

Glu為一種神經傳遞物質(neurotransmitter),從突觸前神經元的突觸小泡(synaptic vesicle)被釋放到突觸間隙(synaptic cleft) 後,除了快速的結合到突觸後神經元的Gllu受體外,約有80%多餘的Glu則會被位於星膠細胞上的Glu轉運蛋白(glutamate transporter)所回收,[此舉可避免過量的Glu聚積在細胞外,造成神經興奮性毒性(excitotoxicity)],藉此星膠細胞將回收的Glu醯胺酸合成酶(glutamine synthetase)的催化下,轉換成醯胺酸(glutamine; Gln),星膠細胞又將Gln釋放到細胞外液中,Gln之後能再被位於Glu神經元及GABA神經元上的醯胺酸轉運蛋白(glutamine transporter)回收到神經細胞內,神經細胞內的Gln則會在醯胺酸酶(glutaminase)的催化下又被轉變為Glu,這整個過程,就是所謂神經細胞與星膠細胞之間的醯胺酸麩胺酸循環(Gln-Glu cycleGGC)(如下圖示)

圖示麩胺酸神經元(glutamatergic)突觸小泡內麩胺(glutamate; Glu)的貯存量受到星膠細胞回收Glu,進一步,合成醯胺酸(glutamine; Gln)的量及分別受到位於星型膠細胞及Glu神經元上的醯胺酸轉運蛋白(SN-1SA-1),其轉運Gln的能力,意即醯胺酸麩胺酸循環(Gln-Glu cycle GGC)的效能所調控。

有趣的是,由於Glu是合成丙基丁酸(GABA)的前身物質(precursor),因此由GABA神經元回收Gln醯胺酸酶(glutaminase)催化轉變而成的Glu,則會進一步經由麩胺酸脫羧酶(glutamic acid decarboxylase)的催化,而合成GABA,這些GABA則可被送入神經突觸小泡貯存,等待釋放。由於GluGABA分別是哺乳類動物成體中最主要的興奮性及抑制性神經傳導物質,因此任何因素可以影響位於GGC路徑酵素的活性,均可能會影響腦中GluGABA神經元的突觸傳遞效能,進而破壞中樞神經系統興奮性及抑制性神經元的突觸傳遞的平衡性,若此平衡受干擾可能導致中樞神經系統發育異常及疾病,包括:性別分化、 癲癇症、憂鬱症或精神分裂症等。

 

 

研究方法:

  • Quantitative RT-PCR:定量特定腦核區mRNA的表現量。
  • 西方墨點轉漬法(western blotting analysis): 用以定量參予GGC的酵素及轉運蛋白(transporter)的蛋白質含量變化。
  • 免疫化學細胞染色法(immunocytochemistry): 用以定性參予GGC的酵素及轉運蛋白的蛋白質表現或是用以鑑定所記錄神經細胞的種類。
  • 大鼠行為觀察:包括生殖行為的觀察。
  • 腦薄片目視全細胞夾箝電生理紀錄(Visualized whole-cell voltage- or current- clamp recordings):最常用來偵測抑制性及興奮性突觸後電流或電位的變化[Inhibitory and excitatory postsynaptic currents(IPSCs;EPSCs)]。除此之外,又包括記錄:

1.Miniature IPSCs (mIPSCs)miniature EPSCs (mEPSCs):反應靜態(basal level)下突觸小泡內抑制性及興奮性神經傳導物質的含量變化等。

2.Strontium evoked IPSCs Strontium evoked EPSCs; miniature evoked IPSCs (meIPSCs)miniature evoked EPSCs (meEPSCs):反應動態(active state)下突觸小泡內抑制性及興奮性神經傳導物質的含量變化、神經傳導物質的效能及突觸小泡的釋放機率等。

3.Spontaneous IPSCs (sIPSCs)spontaneous EPSCs (sEPSCs)Evoked IPSCs (eIPSCs) evoked EPSCs (eEPSCs)field excitatory postsynaptic potential(fEPSP):測量神經突觸效能的變化(synaptic efficacy)

4.成對刺激(paired-pulse stimulation):決定突觸小泡的釋放機率及突觸前神經元因素是否參與神經突觸效能的變化。

5.Puffed GABA or Glutamate: 決定突觸後神經元因素是否參與神經突觸效能的變化。

6.配對神經元紀錄(pair-recording):直接同時紀錄突觸前後兩個神經元之間的電訊號傳遞。

.膠細胞的基丁酸轉運蛋白電流(astrocytic GABA transporter current),星膠細胞的麩胺酸轉運蛋白電流(astrocytic glutamate transporter current):間接反應神經元興奮後,神經傳導物質GABAGlu釋放到突觸間隙的含量高低。

最近五年所發表論文著作及專利:

Journal Articles (peer-reviewed):

  1. Liang SL, Carlson GC, Coulter DA (2020) Epilepsy-induced reduction in glutamine-glutamate cycle efficacy depletes vesicular release of GABA from hippocampal inhibitory synapses. Neurobiol. Dis. (Submitted)
  2. Liang SL (2018) The glutamine-glutamate cycle regulates synaptic glutamate release in ventrolateral ventromedial nucleus of the hypothalamus of perinatal female rats. J. Neuroendocrinol. 30: e12642.
  3. Liang SL*, Alger BE, McCarthy MM (2014) Developmental increase in hippocampal endocannabinoid mobilization: roles of metabotropic glutamate receptor subtype 5 and phospholipase C. J. Neurophysiol. 112:2605-2615. (*, corresponding author).
  4. Liang SL*, Hsu SC, Pan JT (2014) Involvement of dopamine D2 receptor in the diurnal changes of tuberoinfundibular dopaminergic neuron activity and prolactin secretion in female rats. J. BioMed. Sci. 21:37 (*, corresponding author).
  5. Liang SL*, Pan JT (2012) An endogenous dopaminergic tone acting on dopamine D3 receptors may be involved in diurnal changes of tuberoinfundibular dopaminergic neuron activity and prolactin secretion in estrogen-primed ovariectomized rats. Brain Res. Bull. 87:334-339. (*, corresponding author).

Published Abstracts

  1. Liang SL, Chen RS: Perinatal interruption of glutamine-glutamate cycle (GGC) permanently compromises GGC-dependent basal excitatory and inhibitory synaptic transmissions in the hypothalamic neurons of estrous female rats. The 35th Joint Annual Conference of Biomedical Science, Taiwan, Taipei, Mar 21-22, 2021. (Accepted)
  2. Lin YS, Liang SL: Blockade of neuronal glutamine uptake during brain development differently changes fertility of female rats. The 34th Joint Annual Conference of Biomedical Science, Taiwan, Taipei, Mar 23-24, 2019. PY061.
  3. Lin YS, Liang SL: Neonatal disruptions of the glutamate-glutamine cycle reduce the expression of sexual behavior and fertility of female rats. The 33th Joint Annual Conference of Biomedical Science, Taiwan, Taipei, Mar 24-25, 2018. (PY073; The third place in the poster contest held by The Chinese Physiological Society).

3. Lin YS, Liang SL: Neonatal disruptions of the glutamate-glutamine cycle reduce the expression of sexual behavior and fertility of female rats. The 33th Joint Annual Conference of Biomedical Science, Taiwan, Taipei, Mar 24-25, 2018. (PY073).

4. Tong YS, Hwang LL, Chen CY, Liang SL: Different regulations of CART peptides on firing rates and synaptic inputs of DMV neurons innervating stomach and cecum in rats. The 32th Joint Annual Conference of Biomedical Science, Taiwan, Taipei, Mar 25-26, 2017. (PY060).

5. Tong YS , Hwang LL, Chen CY, Liang SL: Retrograde Labeling in vivo of vagal preganglionic neurons innervating stomach and cecum in rats by the carbocyanine dye DiO. The 31th Joint Annual Conference of Biomedical Science, Taiwan, Taipei, Mar 26-27, 2016. (P138).

6. Yeh CY, Liang SL: Sex differential effects of neonatal pretreatments of fluoroacetate or MSO to disrupt glutamate-glutamine cycle on adult reproductive behaviors in rats. EMBO Conference on neural development- function and dysregulation. Taiwan, Taipei, Dec 4-8, 2015. (p32)

專利:

  1. Liang SL (2017) 利用麩醯胺酸改善性功能障礙(Use of glutamine in improving sexual dysfunction.)。台灣,中華民國。專利號碼:發明第I652059號。

中文期刊:

  1. 梁淑鈴 (2011, 十月):簡介腦神經疾病與星狀膠細胞麩胺酸麩胺醯胺循環異常的關連。長庚醫訊,32卷10期,增刊第54-57頁。

獲獎紀錄:

  1. 林毓雄,梁淑鈴 Neonatal disruptions of the glutamate-glutamine cycle reduce the expression of sexual behavior and fertility of female rats.長庚大學生物醫學研究所碩士論文競賽(壁報+口頭報告)第二名。Taiwan, Tau-Yuan, Jul 2-6, 2018. (2C09).
  2. 林毓雄,梁淑鈴Neonatal disruptions of the glutamate-glutamine cycle reduce the expression of sexual behavior and fertility of female rats.中華民國第三十三屆生物醫學聯合學術年會中國生理學會壁報論文競賽第三名。Taiwan, Taipei, Mar 24-25, 2018. (PY073).
  3. 童詠聖,黃玲玲,陳志彥,梁淑鈴 Different regulations of CART peptides on firing rates and synaptic inputs of DMV neurons innervating stomach and cecum in rats. 中華民國第三十二屆生物醫學聯合學術年會中國生理學會壁報論文競賽第三名。 Taiwan, Taipei, Mar 25-26, 2017. (PY060).
  4. The Marsden Fund Referee, The Marsden Fund is affiliated by New Zealand government and is administered by the Royal Society of New Zealand. 2014.
  5. Editorial Board Member in Journal “Animal Cells and Systems”, The official journal of the Korean Society for Integrative Biology. 2010~2013.
  6. 國科會傑出優秀人才獎National Science Council Outstanding Research Award, 2011.

國際交流:

1. 癲癇的研究計畫正與美國賓州大學暨費城兒童醫院的Coulter, D.A., Ph.D. (Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Division of Neurology and the Pediatric Regional Epilepsy Program, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA)實驗室合作進行中

 

 

 

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