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アルツハイマー病、他の認知症、老化 2
Alzheimer's Disease, Other Dementia, Aging 2

開催日 2014/9/11
時間 15:00 - 16:00
会場 Room I(311+312)
Chairperson(s) 山田 麻紀 / Maki K. Yamada (東京大学 大学院医学系研究科 代謝生理化学分野 / Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Japan)
西村 正樹 / Masaki Nishimura (滋賀医科大学分子神経科学研究センター / Moleculer Neuroscience Research Center, Shiga University of Medical Science, Japan)

The effect of DcR3 on modulating microglia activation phenotypes and cognitive functions in Alzheimer’s disease animal model

  • O1-I-4-2
  • Irene Cheng:1  Yi-ling Liu:1 
  • 1:National Yang Ming University, Taiwan 

The effect of DcR3 on modulating microglia activation phenotypes and cognitive functions in Alzheimer's disease animal model

Irene H Cheng, Yi Ling Liu

Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan

The deposition of amyloid β peptide (Aβ), which is generated from amyloid precursor protein (APP), is the pathological hallmark of Alzheimer's disease (AD). Chronic activation of microglia plays dual roles by regulating brain inflammatory responses in the pathogenesis of AD. The ratio of M1/M2 subtypes of microglia can either turn to the neurotoxic or neuroprotective processing under the disease state. Decoy receptor 3 (DcR3) is able to skew the macrophages differentiation into anti-inflammatory subtypes by the neutralization ability under inflammation reaction. Thus, we hypothesize that overexpressing DcR3 in could ameliorate functional and pathological deficits in the AD mouse model. Here, we use both in vitro and in vivo system to identify the role of DcR3 on Aβ-induced neuroinflammation and ameliorate AD-like neuropathology. For in vitro system, conditioned media from primary microglia culture treated with Aβ and DcR3 were used to test their toxicity to primary cortical neuron. For in vivo system, female DcR3 transgene mice were crossed with male APP transgenic mice to generate 4 genotypes of mice. DcR3/APP double transgenic mouse had lower total Aß burden, increased M2a subtype of microglia than APP transgenic mice and showed improvement on cognitive function. In vitro study also demonstrated that the DcR3 can reduce cytokine toxicity in the Aß treated primary neuron. Furthermore, a negative correlation was found between serum DcR3 concentration and total Aß level in AD patients. The immune inhibition role of DcR3 on Aß clearance, microglia phenotype changes, and functional amelioration may be a potential therapeutic strategy for AD-like pathogenesis.

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