林惠菁
專任教授
02-2826-7944
hclin7@nycu.edu.tw【FB粉絲團 https://www.facebook.com/profile.php?id=100075885976029】
動物行為、電生理學、神經訊息傳遞
學歷
| 年度 | 學校名稱 | 學位 |
|---|---|---|
| 1998 | 台北醫學大學藥學系 | 藥學士 |
| 2000 | 國立成功大學藥理所 | 碩士 |
| 2008 | 國立成功大學基礎醫學所 | 博士 |
經歷
| 年度 | 服務機關名稱 | 單位 | 職務 |
|---|---|---|---|
| 2022-迄今 | 國立陽明交通大學 | 國際事務處 | 境外一組組長 |
| 2022-迄今 | 國立陽明交通大學 | 生理學科暨生理學研究所 | 教授 |
| 2019-2021 | 國立陽明大學 | 生理學科暨研究所 | 教授 |
| 2016-2019 | 國立陽明大學 | 生理學科暨研究所 | 副教授 |
| 2011-2016 | 國立陽明大學 | 生理學科暨研究所 | 助理教授 |
| 2008-2011 | 國立成功大學 | 藥理所 | 博士後研究員 |
| 2011 | 法國馬賽國家衛生暨醫學研究院 | 訪問博士後研究員 | |
| 2010 | 美國德州貝勒醫學中心 | 小兒研究部門 | 訪問博士後研究員 |
| 2000-2003 | 基隆長庚 | 藥劑部 | 藥師 |
代表著作
| 排序編號 | 著作名稱 |
|---|---|
| 1 | Chu MC, Wu HF, Lee CW, Chung YJ, Chi H, Chen PS*, Lin HC*. Generational synaptic functions of GABAA receptor β3 subunit deteriorations in an animal model of social deficit. Journal of Biomedical Science. 2022 Jul 29 :51. doi: 10.1186/s12929-022-00835-w |
| 2 | Gan YL, Wang CY, He RH, Hsu PC, Yeh HH, Hsieh TH, Lin HC, Cheng MY, Jeng CJ, Huang MC, Lee YH. FKBP51 mediates resilience to inflammation-induced anxiety through regulation of glutamic acid decarboxylase 65 expression in mouse hippocampus J Neuroinflammation 2022 Jun 19(1):152. doi: 10.1186/s12974-022-02517-8. |
| 3 | Li CT, Juan CH, Lin HC, Cheng CM, Wu HT, Yang BH, Tsai SJ, Su TP, Paul B Fitzgerald Cortical excitatory and inhibitory correlates of the fronto-limbic circuit in major depression and differential effects of left frontal brain stimulation in a randomized sham-controlled trial. Journal of Affective Disorders. 2022 Aug 311:364-370. doi: 10.1016/j.jad.2022.05.107 |
| 4 | Lee CW, Wu HF, Chu MC, Chung YJ, Li CT*, Lin HC* Mechanism of intermittent theta-burst stimulation in synaptic pathology in the prefrontal cortex in an antidepressant-resistant depression rat model. Cerebral Cortex. 2020 (in press) *co-corresponding author. |
| 5 | Chu MC, Lee JY, Lee HF, Chu KW, Wu HF, Lee CW, Lin CH, Tang CW*, Lin HC*. Increased GABAergic inhibitory function against ischemic long-term potentiation in the CA1 region of the hippocampus. Biochem Biophys Res Commun. 2020 Mar 29. pii: S0006-291X(20)30601-X. *co-corresponding author. |
| 6 | Wu HF, Lu TY, Chu MC, Chen PS, Lee CW, Lin HC*. Targeting the inhibition of fatty acid amide hydrolase ameliorate the endocannabinoid-mediated synaptic dysfunction in a valproic acid-induced rat model of Autism. Neuropharmacology. 2020 Jan 162:107736 |
| 7 | Chang CW, Lo YC, Lin SH, Yang SH, Lin HC, Lin TC, Li SJ, Hsieh CC, Ro V, Chung YJ, Chang YC, Lee CW, Kuo CH, Chen SY, Chen YY. Modulation of Theta-Band Local Field Potential Oscillations Across Brain Networks With Central Thalamic Deep Brain Stimulation to Enhance Spatial Working Memory. Front Neurosci. 2019 Nov 26;13:1269 |
| 8 | Lin TC#, Lo YC#, Lin HC#, Li SJ, Lin SH, Wu HF, Chu MC, Lee CW, Lin IC, Chang CW, Liu YC, Chen TC, Lin YJ, Ian Shih YY, Chen YY.MR imaging central thalamic deep brain stimulation restored autistic-like social deficits in the rat. Brain Stimul. 2019 Nov – Dec;12(6):1410-1420. |
| 9 | Jeng JS, Li CT, Lin HC, Tsai SJ, Bai YM, Su TP, Chang YW, Cheng CM. Antidepressant-resistant depression is characterized by reduced short- and long-interval cortical inhibition. Psychological Medicine. 2019 Jun 3:1-7. |
| 10 | Lee CW, Chen YJ, Wu HF, Chung YJ, Lee YC, Li CT*, Lin HC*. Ketamine ameliorates severe traumatic event-induced antidepressant-resistant depression in a rat model through ERK activation. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar ;93:102-113. |
| 11 | Wu HF, Chen YJ, Chu MC, Hsu YT, Lu TY, Chen IT, Chen PS, Lin HC*. Deep Brain Stimulation Modified Autism-like Deficits via the Serotonin System in a Valproic Acid-Induced Rat Model. International Journal of Molecular Sciences. 2018 Sep; 19(9) pii: E2840. |
| 12 | Kuo CJ, Huang CC, Chou SY, Lo YC, Kao TJ, Huang NK, Lin C, Lin HC, Lin HC*, Lee YC*. Potential therapeutic effect of curcumin, a natural mTOR inhibitor, in tuberous sclerosis complex. Phytomedicine. 2019 Feb;54:132-139. *co-corresponding authors. |
| 13 | Lee YC, Huang WC, Lin JH, Kao TJ, Lin HC, Lee KH, Lin HC, Shen CJ, Chang WC, Huang CC. Znf179 E3 ligase-mediated TDP-43 polyubiquitination is involved in TDP-43- ubiquitinated inclusions (UBI) (+)-related neurodegenerative pathology. Journal of Biomedical Science. 2018 Nov 8;25(1):76. |
| 14 | Lee HT, Lee KI, Lin HC, Lee TS. Genetic Deletion of Soluble Epoxide Hydroxylase Causes Anxiety-Like Behaviors in Mice. 2018 Jul Molecular Neurobiology.doi: 10.1007/s12035-018-1261-z. |
| 15 | Wu HF, Chen PS, Hsu YT, Lee CW, Wang TF, Chen YJ, Lin HC. D-Cycloserine ameliorates autism-like deficits by removing GluA2-containing AMPA receptors in a valproic acid-induced rat model. Molecular Neurobiology. 2018 Jun;55(6):4811-4824. |
| 16 | Chang LH, Lin HC, Huang SS, Chen IC, Chu KW, Chih CL, Liang YW, Lee YC, Chen YY, Lee YH, Lee IH. Blockade of soluble epoxide hydrolase attenuates post-ischemic neuronal hyperexcitation and confers resilience against stroke with TrkB activation. Scientific Reports . 2018 Jan 8;8(1):118. |
| 17 | Yeh CH, Hsieh LP, Lin MC, Wei TS, Lin HC, Chang CC, Hsing CH. Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness behavior, and anhedonia. PLoS One 2018, Jan;13 (1):e0191070. |
| 18 | Wu HF, Chen PS, Chen YJ, Lee CW, Chen IT, Lin HC*. Alleviation of N-methyl-D-aspartate Receptor-Dependent Long-term depression via regulation of the Glycogen Synthase Kinase-3β pathway in the amygdala of a valproic acid-induced animal model of autism. Molecular Neurobiology 2017 Sep; 54(7), 5264-5276. |
| 19 | Wu HF#, Chen YJ#, Wu SZ, Lee CW, Chen IT, Lee YC, Huang CC, Hsing CH, Tang CW, Lin HC*. Soluble epoxide hydrolase inhibitor and 14, 15-epoxyeicosatrienoic acid-facilitated long-term potentiation through cAMP and CaMKII in the hippocampus. Neural Plasticity. 2017 Jul. #equal contribution. |
| 20 | Huang HJ, Wang YT, Lin HC, Lee YH, Lin AM. Soluble Epoxide Hydrolase Inhibition Attenuates MPTP-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System: Involvement of α-Synuclein Aggregation and ER Stress. Molecular Neurobiology. 2017Aug. DOI: 10.1007/s12035-017-0726-9. |
| 21 | Wang CF, Yang SH, Lin SH, Chen PC, Lo YC, Pan HC, Lai HY, Liao LD, Lin HC, Chen HY, Huang WC, Huang WJ, Chen YY. A proof-of-principle simulation for closed-loop control based on preexisting experimental thalamic DBS-enhanced instrumental learning. Brain Stimulation 2017 Feb. pii: S1935-861X(17) 30611-3. |
| 22 | Lee KI, Lin HC, Lee HT, Tsai FC, Lee TS. Loss of transient receptor potential ankyrin 1 channel deregulates emotional, social, cognitive, learning and memory development. Molecular Neurobiology 2017 Jul;54(5):3606-3617. |
| 23 | Wang YT, Lin HC, Zhao WZ, Huang HJ, Lo YL, Wang HT, Lin AM. Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death. Scientific Reports . 2017 Apr 12;7:45741. |
| 24 | Tsou JH, Yang YC, Pao PC, Lin HC, Huang NK, Lin ST, Hsu KS, Yeh CM, Lee KH, Kuo CJ, Yang DM, Lin JH, Chang WC, Lee YC. Important roles of Ring Finger Protein 112 in embryonic vascular development and brain function. Molecular Neurobiology. 2017 Apr;54(3):2286-2300. |
| 25 | Li CT, Lu CF, Lin HC, Huang YZ, Juan CH, Su TP, Bai YM, Chen MH, Lin WC. Cortical inhibitory and excitatory function in drug-naive generalized anxiety disorder. Brain Stimulation 2016 Dec. pii: S1935-861X(16) 30389-8. |
| 26 | Yang SH, Chen YY, Lin SH, Liao LD, Lu HS, Wang CF, Chen PC, Lo YC, Phan TD, Chao HY, Lin HC, Lai HY, Huang WC. A sliced inverse regression (SIR) decoding the forelimb movement from neuronal spikes in the rat motor cortex. Frontiers in Neuroscience.2016 Nov. doi: 10.3389/fnins.2016.00556 |
| 27 | Chang CF, Lee YH, Lee KH, Lin HC, Chen CL, Shen CK, Huang CC. Therapeutic effect of berberine on TDP-43-related pathogenesis in FTLD and ALS. Journal of Biomedical Science 2016 Oct; 23:72. |
| 28 | Lee KI, Lee HT, Lin HC, Tasy HJ, Tsai FC, Shyue SK, Lee TS. Role of transient receptor potential Ankyrin 1 channels in Alzheimer’s disease. Journal of Neuroinflammation 2016 Apr; 13(1): 92. doi: 10.1186/s12974-016-0557-z. |
| 29 | Lee KI, Chiang CW, Lin HC, Zhao JF, Li CT, Shyue SK, Lee TS. Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring. Archives of Toxicology 2016 May; 90(5): 1211-1224. |
| 30 | Lin HC#, Pan HC#, Lin SH, Lo YC, Shen Elise TH, Liao LD, Liao PH, Chien YW, Liao KD, Jaw FS, Chu KW, Lai HY, Chen YY. Central thalamic deep-brain stimulation alters striatal–thalamic connectivity in cognitive neural behavior. #equal contribution. Frontiers in Neural Circuits 2016 Jan 13; 9:87. doi: 10.3389/fncir.2015.00087. #equal contribution. |
| 31 | Wu HF, Yen HJ, Huang CC, Lee YC,Wu SZ , Lee TS, Lin HC*, Soluble epoxide hydrolase inhibitor enhances synaptic neurotransmission and plasticity in mouse prefrontal cortex. Journal of Biomedical Science 2015 Oct; 22:94. doi: 10.1186/s12929-015-0202-7. SCI. |
| 32 | Lin HC#, Li CT#, David Tan TW, Cheng CW, Chou TK, Kong FL, Yu TH, Huang WS, Su DP, Liu RS, Skye Yeh HH. Non-linear alteration of serotonin transport availability in posttraumatic stress disorder measured with 4- [18F]ADAM positron emission tomography. Current Molecular Imaging 2015; 4: 57-64. #equal contribution. |
| 33 | Wang CY, Lin HC#, Song YP#, Hsu YT#, Lin SY, Hsu PC, Lin CH, Hung CC, Hsu MC, Kuo YM, Lee YJ, Hsu CY, Lee YH. 2015. Protein kinase C dependent growth-associated protein 43 phosphorylation regulates gephyrin aggregation at developing GABAergic synapses. Molecular and Cellular Biology 2015 May; 35(10):1712-1726. #equal contribution. |
| 34 | Chen YW, Lin HC,Ng MC, Hsiao YH, Wang CC, Gean PW, Chen PS. Activation of mGluR2/3 underlies the effects of N-acetylcystein on amygdala associated autism-like phenotypes in a valproate-induced rat model of autism. Frontiers in Behavioral Neuroscience. 2014 Jun; 8: 219 |
| 35 | Wang CC#, Lin HC#, Chan YH, Gean PW, Yang YK, Chen PS. (2013). 5-HT1A-receptor agonist modified amygdala activity and amygdala-associated social behavior in a valproate-induced rat autism model. International Journal of Neuropsychopharmacology 2013 Oct; 16(9):2027-2039. # equal contribution. |
| 36 | Lin HC, Gean PW, Wang CC, Chan YH, Chen PS. The Amygdala Excitatory/Inhibitory Balance in a Valproate-induced Rat Autism Model. PLoS One 2013, Jan; 8(1):e55248. |
| 37 | Lin HC, Tseng YC, Mao S, Gean PW. GABAA receptor endocytosis in the basolateral amygdala is critical to the reinstatement of fear memory measured with fear-potentiated startle. The Journal of Neuroscience 2011 Tun; 31(24):8851-8861. |
| 38 | Lin HC, Mao SC, Su CL, Gean PW. Alterations of excitatory transmission in the lateral amygdala during expression and extinction of fear memory. International Journal of Neuropsychopharmacology 2010 Apr; 13(3):335-345. |
| 39 | Lin HC, Mao SC, Su CL, Gean PW. The role of prefrontal cortex CB1 receptors in the modulation of fear memory. Cereb Cortex 2009 Jan;19(1):165-175. |
| 40 | Lin HC, Mao SC, Gean PW. Block of GABAA receptor insertion in the amygdala impairs extinction of conditioned fear. Biological Psychiatry 2009 Oct; 66(7) 665-673. |
| 41 | Mao SC, Lin HC, Gean PW. Augmentation of fear extinction by infusion of glycine transporter blockers into the amygdala. Molecular Pharmacology 2009 Aug; 76(2):369-378. |
| 42 | Lin HC, Mao SC, Chen PS, Gean PW. Chronic cannabinoid administration in vivo compromises extinction of fear memory. Learning & Memory 2008 Dec; 15(12):876-884. |
| 43 | Mao SC, Lin HC, Gean PW. Augmentation of Fear Extinction by D-Cycloserine is Blocked by Proteasome Inhibitors. Neuropsychopharmacology 2008 Dec; 33(13):3085-3095. |
| 44 | Lin HC, Mao SC, and Gean PW. Effects of intra-amygdala infusion of CB1 receptor agonists on the reconsolidation of fear-potentiated startle. Learning & Memory 2006 May; 13(3): 316-321. |
| 45 | Yeh SH, Mao SC,Lin HC, Gean PW. Synaptic expression of glutamate receptor after encoding of fear memory in the rat amygdala. Molecular Pharmacology 2006 Jan; 69(1): 299-308. |
| 46 | Lin HC, Wang SJ, Luo MZ, Gean PW. Activation of group II metabotropic glutamate receptors induces long-term depression of synaptic transmission in the rat amygdala. The Journal of Neuroscience. 2000 Dec; 20(24): 9017–9024. |
五年內執行計畫
| 排序編號 | 年度 | 計畫名稱 | 單位 | 計畫期間 |
|---|---|---|---|---|
| 1 | – | 以突觸抑制功能為基礎評估有效治療難治型憂慮症之機轉與標的 | 科技部 | – |
| 2 | – | 以大腦FKBP5 為標的: 中風後病生理與神經調節機制研究整合型計畫–FKBP5 在中風神經塑性之角色：著重缺血性損傷和神經刺激介入的作用 | 科技部整合型計畫 | – |
| 3 | 類長期增益之突觸塑性作為難治型憂鬱症動物模式之治療指標:非侵入性之重覆透顱磁刺激與抑制可溶環氧化物水解酶 | 科技部-優秀年輕學者研究計畫 | ||
| 4 | 壓力誘發動物情緒失調之突觸機制:藥物和電刺激治療 | 科技部-傑出學者養成計畫 |
實驗室成員
| 職稱/學位 | 姓名 |
|---|---|
| 博士後研究員 | 李旂緯 |
| 博士生 | 劉沛勳、初銘家、張景翔 |
| 碩士生 | 柯佳辰、吳麒均、李佳怡、吳靖堯、鍾婷羽、李琬柔、黃湘菱、鄭鳳婷、吳羿帆 |
| 大學部 | 曾宇佑、賈舒叡、陳玉鳳、羅依璿、蘇善宇 |
| 研究助理 | 吉翔 |
| 實驗室畢業生(博士班) | 吳函芳、李旂緯 |
| 實驗室畢業生(碩士班) | 翁崇瀚、許雅婷、吳函芳、顏欣如、朱凱文、陳怡如、李旂緯、陳翊端、呂亭儀、鍾岳融、張芸綺、謝宗翰、高珮瑜、張傑宥、彭子寧、楊子瑢 |
| 實驗室畢業生(大學部) | 陳怡婷、楊巧慈、宋瑋倫、周芸綺、李淯瑄 |
實驗室活動
研究方向
本實驗室以疾病動物模式進行精神生物醫學與藥物學結合的轉譯醫學研究，主要研究方向如下：
一、憂慮症
憂鬱症是造成社會經濟負擔的精神疾患。雖已有百憂解等臨床藥物，但仍有30%以上的病患處於對憂鬱藥物治療無效的情況。這類對抗憂鬱藥物有阻抗的病患被稱之為頑固型憂鬱症，也是目前臨床治療的一大困境。因此，探討頑固型憂鬱症的致病機轉，並尋找其有效的治療手段是迫切需要的。我們成功以創傷壓力建立對於百憂解等臨床一線抗憂鬱劑具有阻抗性，但對低劑量k他命治療有反應的動物模式。發現頑固型憂鬱症的動物會出現前額葉皮質功能缺損，與杏仁核功能亢進的情況。這項實驗結果與我們合作的臨床團隊的病患數據有著高度相似性(Lee CW et al., Prog Neuropsychopharmacol Biol Psychiatry. 2019)。
近年來我們也與台北榮總臨床合作進行非侵入性的治療—重複透顱磁刺激(repetitive transcranial magnetic stimulation，rTMS)，運用在臨床病患與動物模式的治療。臨床團隊的發現中以證實rTMS的新形的療程間歇性theta波經顱磁刺激(intermittent theta burst stimulation，iTBS)具有良好的治療效果，且此項治療的應用更獲得台灣食品藥物管理署的核准用於各大醫院。我們探討iTBS治療頑固型憂鬱症動物模式的機轉，發現iTBS的治療可以改善神經突觸可塑性的異常，在分子機制上，iTBS可藉由調控腦源性神經營養因子(brain-derived neurotrophic factor，BDNF)，達到改善憂鬱之行為與神經突觸可塑性的異常(Lee CW et al., Cerebral Cortex. 2021)。
此外，我們也進一步比較另一種rTMS的療程持續性theta波經顱磁刺激(continuous theta burst stimulation，cTBS)，結果發現，cTBS的治療亦可改善頑固型憂鬱症動物模式憂鬱行為。然而在機轉方面，cTBS僅能改善抑制型相關的神經突觸可塑性的異常，且僅能調控proBDNF的表現，達到改善憂鬱之行為(Lee CW et al., Experimental Neurology. 2023)。我們未來將以藥物學角度切入，檢測新合成的新穎藥物用於頑固型憂鬱症的療效。
綜上所述，現今生活型態改變導致生活壓力增加，憂鬱症的盛行率也隨之增高，對於治療頑固型憂鬱症的研究更顯重要。我們未來將嘗試尋找頑固型憂鬱症治病的關鍵神經傳遞物質。並以此為標的，與臨床團隊共同尋找有效的治療方式與臨床治療有效性的預測。
二、自閉症
自閉症是一種神經發育疾病，大腦興奮性及抑制性神經傳導的失衡及突觸功能或結構的缺失，是造成自閉症病徵(社交障礙、溝通缺失及固著/重複行為)的主因。我們的研究主要透過表現類自閉症行為之齧齒類動物，探討造成自閉症大腦缺損的病理機轉，並試圖從中尋找自閉症的治療手段，造福飽受疾病所困的自閉症患者。
我們以藥物學的角度，針對臨床藥物和調控大腦麩胺酸(glutamate)系統中N-methyl-D-aspartate(NMDA)受體所媒介的興奮性突觸可塑性，發現無論是直接部分阻斷NMDA受體，或是間接調控其下游之分子機制，均成功改善自閉鼠的行為表徵 (Wu HF et al., Molecular Neurobiology. 2017; Wu HF et al., Molecular Neurobiology. 2018)。以臨床使用電刺激角度切入，我們藉由腦深層電刺激(deep brain stimulation)在大腦形成之超微型電流迴路，調控大腦神經傳導平衡，改善動物的自閉表徵(Wu HF et al., International Journal of Molecular Sciences. 2018)。
鑑於大腦早期發育受到外在環境毒物的曝露與精神疾病的盛行率驟增息息相關，我們最近探討環境因素對自閉症的影響，發現第一子代自閉鼠的社交缺失及大腦突觸抑制與興奮性調節異常會延續至第二子代鼠，並發現突觸抑制性系統的恆定在維護跨世代社交功能之重要價值(Chu MC et al., Journal of Biomedical Science. 2022)。未來將嘗試探討發育階段，進而尋找自閉症致病的核心機制與治療手段。。
我們團隊建立以精神醫學或發育領域的動物疾病模式，與臨床醫學攜手尋找治療有效的嶄新標的和機轉，未來我們也將結合鈣離子呈像、化學遺傳學及光遺傳學技術，將研究層次自微型突觸結構及單一腦區，提升至大腦特定神經迴路與疾病行為相關性之解析，並藉此研發新穎藥物和新興治療策略的運用於臨床，期能治療大腦疾患並降低社會醫療之負擔。歡迎對精神生物醫學領域和神經科學領域有興趣的同學加入團隊。