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Behavioural deficits in transgenic mice expressing human truncated (1-120 amino acid) alpha-synuclein.


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Authors

Yang, Sujeong 
Sauchanka, Olga 
Spillantini, Maria Grazia 
Anichtchik, Oleg 

Abstract

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 II 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.

Description

Keywords

Alpha-synuclein, Dementia with Lewy bodies, Memory, Neurodegeneration, Transgenic mouse, Age Factors, Animals, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Disease Models, Animal, Exploratory Behavior, Gene Expression Regulation, Humans, Lewy Body Disease, Male, Maze Learning, Mice, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Prosencephalon, RNA, Messenger, alpha-Synuclein

Journal Title

Exp Neurol

Conference Name

Journal ISSN

0014-4886
1090-2430

Volume Title

264

Publisher

Elsevier BV
Sponsorship
Parkinson's UK (None)
Parkinson's UK (None)
This work was performed with funds obtained from Alzheimer’s Research UK (grants ART-SRF2010-1, ART-PPG2009B-1).