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Institute of Neuroscience, NYMU
Hey-Jen Tsay Professor

Laborataory of Neural Development and Regeneration

Hey-Jen Tsay Professor

hjtsay@ym.edu.tw

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

Fax:+886-2-2820-0259

Ph.D., Dept. Biochemistry
New York State University at Stony Brook

 

Research Interest

Our research interest is focused on the role of microglia at the late stage and early stage of Alzheimer’s disease (AD).  At the late stage, overactivated microglia clustering at neuritic plaques constantly release neurotoxins, which actively contribute to progressive neurodegeneration in AD.  Therefore, attenuating microglia clustering can reduce the focal neuroinflammation at neuritic plaques.  We have identified CCL5 and CCL2 as prominent chemokines mediating the chemotactic migration of microglia toward Abeta aggregates. We find that TGF-beta1 reduces Abeta-induced microglial chemotaxis through the SMAD2 pathway.  The down-regulation of CCL5 by TGF-beta1, at least, partially contributes to the clustering of microglia at Abeta aggregates.  TGF-beta1 may ameliorate microglia-mediated neuroinflammation in AD by preventing activated microglia clustering at neuritic plaques.

 
At the early stage, the accumulation of soluble oligomeric amyloid-beta peptide prior to the presence of senile plaques contributes to synaptic and memory deficits in AD. Although microglia are prominent on oAbeta uptake in CNS, the mechanism of mediating microglial oAbeta clearance remains unclear.  Our study suggests that scavenger receptor at the plasma membrane and lysosomal capthesin B are critical for microglial oAbeta clearance.  This study provides the first insight into how microglia are involved in the clearance of oAbeta and their roles at the early stages of AD.

More than 95% of AD are sporadic without familial history.  During the aging process, vesicular damages are associated with sporadic AD.  Our recent project is focused on establishing stroke animal models and ask the impact of vesicular damages on the initiation of AD . 

 

Invited Lectures/Publications

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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