Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann-Pick disease type C

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	Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann-Pick disease type C
	Chen, Gang ; Li, Hai-Min ; Chen, Yi-Ren ; Gu, Xiao-Song ; Duan, Shumin
刊名	GLIA
	2007
卷号	55 期号:15 页码:1509-1518
关键词	Niemann-Pick disease type C astrocyte estradiol neuronglia interaction neurodegenerative disease ACUTE REGULATORY PROTEIN MURINE MODEL NEURONAL DEGENERATION ALZHEIMERS-DISEASE CHOLESTEROL HOMEOSTASIS CNS SYNAPTOGENESIS CELL-DEATH MICE EXPRESSION GLIA
ISSN号	0894-1491
通讯作者	Gu, XS (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai, Peoples R China,neurongu@public.nt.js.cn ; shumin@ion.ac.cn
英文摘要	Niemann-Pick disease type C (NPC) is a deadly neurodegenerative disease often caused by mutation in a gene called NPC1, which results in the accumulation of unesterified cholesterol and glycosphingolipids in the endosomal-lysosomal system. Most studies on the mechanisms of neurodegeneration in NPC have focused on neurons. However, the possibility also exists that NPC1 affects neuronal functions indirectly by acting on other cells that are intimately interacting with neurons. In this study, using a heterotypic neuron-glia coculture system, we found that wild-type neurons cultured on a layer of NPC1-/- astrocytes showed decreased neurite growth compared with those cultured on wild-type astrocytes. RT-PCR and immunohistochemical assessments showed significantly lower expression of neurosteroid enzymes and StAR (steroidogenic acute regulatory protein) in NPC1-/- astrocyte cultures than in wild-type cultures. Furthermore, a reduced level of estradiol was measured from both astrocyte culture medium and whole brains from NPC1-/- mice. Administration of 17 beta-estradiol to neonatal NPC1-/- mice significantly delayed the onset of neurological symptoms, increased Purkinje cell survival, and extended the animals' life span. Our findings suggest that astrocyte dysfunction contributes to the neurodegeneration of NPC and estradiol treatment may be useful in ameliorating progression of the disease. (C) 2007 Wiley-Liss, Inc.
学科主题	Neurosciences & Neurology
收录类别	SCI
语种	英语
公开日期	2012-07-23
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1747]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Chen, Gang,Li, Hai-Min,Chen, Yi-Ren,et al. Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann-Pick disease type C[J]. GLIA,2007,55(15):1509-1518.
APA	Chen, Gang,Li, Hai-Min,Chen, Yi-Ren,Gu, Xiao-Song,&Duan, Shumin.(2007).Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann-Pick disease type C.GLIA,55(15),1509-1518.
MLA	Chen, Gang,et al."Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann-Pick disease type C".GLIA 55.15(2007):1509-1518.