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國立陽明大學神經科學研究所
從分子到認知
分類清單
蔡惠珍 教授

神經發育及退化研究室

蔡惠珍 教授(專任)

hjtsay@ym.edu.tw

Tel:+886-2-2826-7000#5033

Fax:+886-2-2820-0259

紐約州立大學石溪分校細胞及生物化學博士

 

成員

李以恆(博士班) 洪漢鐘(碩士班) 陳立民(碩士班) 

高培甄(研究助理) 許書夢(研究助理)

 

合作研究

謝奉勳 國家衛生研究院 博士 

蕭永基 國家中醫藥研究所 博士

 

研究簡介

阿茲海默症(AD)是一種病因不明的漸進式神經退化性疾病。在AD病患與AD基因轉殖小鼠都觀察到胰島素抗性與神經系統發炎反應。代謝症候群和血管的病變可能是AD的危險因子,為了研究高脂食物引起的代謝壓力對AD病情的影響,我們建立了一個AD基因轉殖鼠的動物模式用HFD加鏈脲佐黴素(STZ)協同地加劇小鼠的高醣血症和葡萄糖不耐受性。我們探討APP/PS1基因轉殖小鼠(AD mice) 在AD早期病程高脂飲食(HFD)對Ab負荷及神經膠細胞活化的影響。結果顯示周邊代謝壓力與AD中樞的病徵會互相加重彼此病情的惡化,HFSTZ加劇AD小鼠體重增加、葡萄糖不耐受性與胰島素抗性,HFSTZ AD小鼠的肝臟有較高脂質不正常堆積,產生非酒精性脂肪肝。這研究闡述了AD的中樞神經系統會加劇周邊胰島素抗性,證明了AD pathology加劇HFD誘發的周邊組織代謝壓力(Obesity and hepatic steatosis are associated with elevated serum amyloid beta in metabolically stressed APPswe/PS1dE9 Mice. Plosone, 2015)。

HFSTZ引起的代謝壓力增加AD小鼠中樞神經系統的老年斑塊數目和面積、活化星狀膠細胞並延長AD小鼠築巢完成時間,顯示HFSTZ進一步損傷了AD小鼠的認知能力,所以AD的基因型加劇高脂飲食對中樞的傷害(Aggravated cognitive dysfunction and impaired cerebral glucose regulation are associated with astrocytic activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice. Neurobiology of Disease, 2015)。因此周邊的胰島素抗性及AD中樞的病變互為因果,彼此加重對方的影響力。最近我們發表了兩篇應用活血化瘀傳統複方及具降血糖功能的黃耆多醣水萃物減輕阿滋海默症病情的研究。

現代西式飲食富含高脂及高糖的成分,增加糖尿病的罹患率,而糖尿病又與AD有很高的共病關係,因此我們分別購買高脂及高蔗糖飼料餵養AD轉殖鼠,並觀察到AD鼠與野生鼠其維持能量恆定的下視丘腦區發生差異性的傷害,目前機制性的結果正在投稿中。

 

(圖一:阿滋海默症基因轉殖鼠海馬迴中黑色的微膠細胞包圍綠色的老年斑塊的現象)。
 
    圖2          圖3

 

論文

Chih-Wen Yeha, Hui-Kang Liub,c, Lie-Chwen Linb, Kou-Tong Lioud, Yung-Cheng Huange, Chien-Hung Lina, Tsai-Teng Tzengf, Feng-Shiun Shieg, Huey-Jen Tsay* (蔡惠珍), Young-Ji Shiao* (2017) Xuefu Zhuyu decoction ameliorates obesity, hepatic steatosis, neuroinflammation, amyloid deposition and cognition impairment in metabolically stressed APPswe/PS1dE9 mice. Journal of Ethnopharmacology 209 (2017) 50–61

Chang CC†, Yuan W†, Lin YL, Liu RS, Juan YC, Sun WH,6 Tsay HJ (蔡惠珍) , Huang HC, Lee YC, and Liu HK (2016) Evaluation of the In Vivo therapeutic effects of Radix Paeoniae Rubra Ethanol Extract with the hypoglycemic activities Measured from multiple cell-based assays. Evidence-Based Complementary and Alternative Medicine 25(1):123

Chang CC, Yuan W, Roan HY, Chang JL, Huang HC, Lee YC, Tsay HJ (蔡惠珍) and Liu HK (2016) The ethyl acetate fraction of corn silk exhibits dual antioxidant and anti-glycation activities and protects insulin-secreting cells from glucotoxicity. Complementary and Alternative Medicine 16(1): 432

 Lee KI, Lee HT, Lin HC, Tsay HJ (蔡惠珍), Tsai C, Shyue SK, Lee TS (2016) The Role of transient receptor potential ankyrin 1 channels in Alzheimer’s disease.J Neuroinflammation 13(1): 92.

Tsay HJ (蔡惠珍), Huang YC†, Chen YJ, Lee YH, Hsu SM, Tsai KC, Yang CN, Huang FL, Shie FS, Lee LC, Shiao YJ (2016) Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO. J. Biomedical Sci. 23:27

Shie FS, Shiao YJ, Yeh CW, Lin CH, Tzeng TT, Hsu HC, Huang FL, Tsay HJ* (蔡惠珍), Liu HK* (2015) Obesity and hepatic steatosis are associated with elevated serum amyloid beta in metabolically stressed APPswe/PS1dE9 Mice. Plos One 10(8):e0134531

Yeh CW, Skye Yeh HH, Shie FS, Lai WS, Liu HK , Tzeng TT, Tsay HJ * (蔡惠珍) , and Shiao YJ *(2015) Aggravated cognitive dysfunction and impaired cerebral glucose regulation are associated with astrocytic activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice. Neurobiology of Aging 2015 36(11): 2984-94. 

Lin YL †, Tsay HJ † (蔡惠珍), Lai TH, Tzeng TT and Shiao YJ * Lithospermic acid attenuates1-methyl-4-phenylpyridine -induced neurotoxicity by blocking neuronal apoptotic and neuroinflammatory pathways. J. Biomedical Sci. 22:37.

Tzeng TT, Tsay HJ (蔡惠珍), Chang L, Hsu CL, Lai TH, Huang FL, and Shiao YJ* (2014) Caspase 3 involves in neuroplasticity, microglial activation, and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid. J. Biomedical Sci. 20:9

Tsay HJ (蔡惠珍), Huang YC, Huang FL, Chen CP, Tsai YH, Wang YH, Wu MF, Chiang FY, and Shiao YJ* (2013) Amyloid beta peptide-mediated neurotoxicity is attenuated by the proliferating microglia more potently than by the quiescent phenotype. J. Biomedical Sci. 20:78.

Liu YH, Lai WS, Tsay HJ* (蔡惠珍), Wang TW* and Yu JY* (2013) Effects of prenatal immune activation on adult neurogenesis in the subventricular zone-olfactory bulb pathway and odor discrimination. Schizophrenia Research 151, 1–11.

Huang FL, Shiao YJ, Hou SJ, Yang CN, Chen YJ, Lin CH, Shie FS, Tsay HJ* (蔡惠珍) (2013) Cysteine-Rich domain of scavenger receptor AI modulates the efficacy of surface targeting and mediates oligomeric Ab internalization. J. Biomedical Sci. 20:54. 

Wang CJ, Chen CC, Tsay HJ (蔡惠珍), Chiang  FY , Wu MF , Shiao YJ* (2013) Cudrania cochinchinensis attenuates amyloid β protein-mediated microglial activation and promotes glia-related clearance of amyloid β protein. J. Biomedical Sci. 20:53. 

 Lin YL, Tsay HJ (蔡惠珍), Liao YF, Wu MF, Wang CN, and Shiao YJ* (2012) The components of Flemingia macrophylla attenuates amyloid beta-protein accumulation by regulating amyloid beta-protein metabolic pathway. Evid. based Complement. Alternat. Med. 795843.

Yang DC, Tsai CC, Liao YF, Fu HC, Tsay HJ(蔡惠珍), TF Huang, Chen YH *, Hung SC. (2012) Twist Controls Skeletal Development and Dorsoventral Patterning by Regulating Runx2 in Zebrafish. Plos One

Wang CC, Huang HB , Tsay HJ (蔡惠珍) , Shiao MS, Wu WJ, Cheng YC , Lin TH (2012) Characterization of Aβ aggregation mechanism probed by congo red J Biomol Struct Dyn. 30(2):160-9 

Yang CN, Shiao YJ, Shie FS, Guo BS, Chen PH, Chou CY, Chen YJ, Huang FL, and Tsay HJ: Mechanism mediating oligomeric Abeta clearance by naive primary microglia . Neurobiology of Disease 2011.
 
Huang YC, Chen YC, Tsay HJ, Chyan CL, Chen CY, Huang HB, and Lin TH: The effect of PKA-phosphorylation on the structure of inhibitor-1 studied by NMR spectroscopy. J. Biochem. 147:273-278, 2010.
 
Chen JH, Hsu PC, Wang LW, Tsay HJ, Kan IJ, and Shie FS: Modulation of microglial immune response by a novel thiourea derivative. Chem Biol Interact 2010.
 
Huang WC, Yen FC, Shie FS, Pan CM, Shiao YJ, Yang CN, Huang FL, Sung YJ, and Tsay HJ: TGF-beta1 blockade of microglial chemotaxis toward Amyloid-beta aggregrates involves SMAD signaling and down-regulation of CCL5. J. Neuroinflammation 7:28-38,2010.
 
Huang WC, Yen FC, Shiao YJ , Chan JL, Shie FS, Yang CN, Sung YJ, Huang FL, and Tsay HJ: Enlargement of Amyloid-beta aggregates through chemokine-dependent microglia clustering. Neuroscience Research 63:280-287, 2009.
 
Wu SH, Chen YH, Huang F-L, Chang CH, Chang YF, Tsay HJ: Multiple Regulatory Elements Mediating Neuronal-Specific Expression of Zebrafish Sodium Channel Gene, Scn8aa. Dev. Dyn. 237: 2554-2565, 2008.
 
Yang DC, Tsay HJ, Lin SY, Chiou SH, Li MJ, Chang TJ, and Hung SC: cAMP/PKA Regulates Osteogenesis, Adipogenesis and Ratio of RANKL/OPG mRNA Expression in Mesenchymal Stem Cells by Suppressing Leptin. Plos one 3 (2)1540-1550, 2008.
 
Chen YH, Huang YH, Wang YH, and Tsay HJ: Teratogenic Effects of Caffeine on Zebrafish. Neurotoxicology and Teratology 30:440-447, 2008.
 
Wang YH, Li CK, Lee GH, Tsay HJ, Tsai HJ, and Chen YH: Inactivation of Zebrafish mrf4 Leads to Myofibril Misalignment and Motor Axon Growth Disorganization. Dev. Dyn. 237: 1043-1050, 2008.
 
Chen YH, Huang FL, Cheng YC, Wu CJ, and Tsay HJ: Knockdown of zebrafish Nav1.6 sodium channel impairs embryonic locomotor activities. J. Biomedical Sci. 15: 69-78, 2008.
 
 
 
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