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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.1
- 수록면
- 222 - 231 (10page)
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초록· 키워드
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Parkinson’s disease (PD) is the most prevalent neurodegenerative motor disorder. While PD has been attributed to dopaminergic neuronal death in substantia nigra pars compacta (SNpc), accumulating lines of evidence have suggested that reactive astrogliosis is critically involved in PD pathol ogy. These pathological changes are associated with α-synuclein aggregation, which is more prone to be induced by an A53T mutation. Therefore, the overexpression of A53T-mutated α-synuclein (A53T-α-syn) has been utilized as a popular animal model of PD. However, this animal model only shows marginal-to-moderate extents of reactive astrogliosis and astrocytic α-synuclein accumulation, while these phenomena are prominent in human PD brains. Here we show that Adeno-GFAP-GFP virus injection into SNpc causes severe reactive astrogliosis and exacerbates the A53T α-syn-mediated PD pathology. In particular, we demonstrate that AAV-CMV-A53T-α-syn injection, when combined with Adeno-GFAP-GFP, causes more significant loss of dopaminergic neuronal tyrosine hydroxylase level and gain of astrocytic GFAP and GABA levels. Moreover, the combination of AAV-CMV-A53T-α-syn and Adeno-GFAP-GFP causes an extensive astrocytic α-syn expression, just as in human PD brains. These results are in marked contrast to previous reports that AAV-CMV-A53T-α-syn alone causes α-syn expression mostly in neurons but rarely in astro cytes. Furthermore, the combination causes a severe PD-like motor dysfunction as assessed by rotarod and cylinder tests within three weeks from the virus injection, whereas Adeno-GFAP-GFP alone or AAV-CMV-A53T-α-syn alone does not. Our findings implicate that inducing reactive astrogliosis exacerbates PD-like pathologies and propose the virus combination as an advanced strategy for developing a new animal model of PD.
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참고문헌 (34)
참고문헌 신청
Samii A / 2004 / Parkinson's disease / Lancet 363:1783~1793
Lang AE / 2018 / Disease modification in Parkinson's disease : current approaches, challenges, and future considerations / Mov Disord 33:660~677
Jagmag SA / 2016 / Evaluation of models of Parkinson's disease / Front Neurosci 9:503
Gispert S / 2009 / Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration / PLoS One 4:e5777
Lee MK / 2002 / Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53--> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice / Proc Natl Acad Sci U S A 99:8968~8973
Lang AE / 2018 / Disease modification in Parkinson's disease : current approaches, challenges, and future considerations / Mov Disord 33:660~677
Jagmag SA / 2016 / Evaluation of models of Parkinson's disease / Front Neurosci 9:503
Gispert S / 2009 / Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration / PLoS One 4:e5777
Lee MK / 2002 / Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53--> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice / Proc Natl Acad Sci U S A 99:8968~8973
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