期刊
EXPERIMENTAL NEUROLOGY
卷 264, 期 -, 页码 8-13出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2014.11.003
关键词
Alpha-synuclein; Memory; Dementia with Lewy bodies; Neurodegeneration; Transgenic mouse
资金
- Alzheimer's Research UK [ART-SRF2010-1, ART-PPG2009B-1]
- Alzheimers Research UK [ART-SRF2010-1, ART-PG2011-20, ART-PPG2009B-1] Funding Source: researchfish
- Parkinson's UK [G-0701, G-1102] Funding Source: researchfish
Accumulation and aggregation of alpha-synuclein in cortical and hippocampal areas is a pathological sign for dementia with Lewy bodies (DLB) and Parkinson's disease with dementia. However the mechanisms of alpha-synuclein triggered cellular dysfunction leading to the development of memory impairment is not clear. We have created a mouse model of DLB, where aggregation-prone human truncated (120 amino acid) alpha-synuclein is expressed in forebrain areas under the calcium/calmodulin-dependent protein kinase H alpha (CamKII-alpha) promoter. We have observed the presence of the transgenic protein in target forebrain areas, with small granular cytoplasmic accumulation of aggregated alpha-synuclein. This was associated with a progressive deficit in cortical-hippocampal memory tests including the Barnes maze and novel object recognition. This data suggests that low levels of aggregation prone alpha-synuclein are sufficient to induce memory deficits in mice and that forebrain regions associated with cognitive function may have an increased sensitivity to the truncated toxic form of alpha-synuclein. (C) 2014 Elsevier Inc. All rights reserved.
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