Abstract:
:Niemann-Pick disease type C (NPC) is an inherited lysosomal storage disease characterised by accumulation of cholesterol and glycosphingolipids. NPC patients suffer a progressive neurodegenerative phenotype presenting with motor dysfunction, mental retardation and cognitive decline. To examine the onset and progression of neuropathological insults in NPC we have systematically examined the CNS of a mouse model of NPC1 (Npc1(-/-) mice) at different stages of the disease course. This revealed a specific spatial and temporal pattern of neuropathology in Npc1(-/-) mice, highlighting that sensory thalamic pathways are particularly vulnerable to loss of NPC1 resulting in neurodegeneration in Npc1(-/-) mice. Examination of markers of astrocytosis and microglial activation revealed a particularly pronounced reactive gliosis in the thalamus early in the disease, which subsequently also occurred in interconnected cortical laminae at later ages. Our examination of the precise staging of events demonstrate that the relationship between glia and neurons varies between brain regions in Npc1(-/-) mice, suggesting that the cues causing glial reactivity may differ between brain regions. In addition, aggregations of pre-synaptic markers are apparent in white matter tracts and the thalamus and are likely to be formed within axonal spheroids. Our data provide a new perspective, revealing a number of events that occur prior to and alongside neuron loss and highlighting that these occur in a pathway dependent manner.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Pressey SN,Smith DA,Wong AM,Platt FM,Cooper JDdoi
10.1016/j.nbd.2011.12.027subject
Has Abstractpub_date
2012-03-01 00:00:00pages
1086-100issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(11)00402-5journal_volume
45pub_type
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
pub_type: 杂志文章
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2007.01.006
更新日期:2007-06-01 00:00:00
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journal_title:Neurobiology of disease
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doi:10.1016/j.nbd.2016.03.013
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.06.016
更新日期:2012-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.nbd.2018.03.014
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.01.020
更新日期:2013-06-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.03.004
更新日期:2019-07-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.07.013
更新日期:2006-11-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.03.005
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
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更新日期:2020-08-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.01.013
更新日期:2014-05-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.07.014
更新日期:2017-10-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.10.007
更新日期:2007-02-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.12.022
更新日期:2012-03-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2016-07-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2007.10.005
更新日期:2008-03-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2008.04.007
更新日期:2008-08-01 00:00:00