title: Behavioural deficits in transgenic mice expressing human truncated (1-120 amino acid) alpha-synuclein.
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.
authors.affiliation: Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Hall
authors.affiliation: Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK.
authors.forename: Sujeong
authors.initials: S
authors.lastname: Yang
authors.affiliation: Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Sauchanka
authors.affiliation: Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
authors.affiliation: Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK; Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth University, PL6 8BU, UK. Electronic address: oleg.anichtchik@plymouth.ac.uk.
authors.forename: Oleg
authors.initials: O
authors.lastname: Anichtchik
mesh_terms: D000367:Age Factors; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics*
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D051844:alpha-Synuclein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Alpha-synuclein; Dementia with Lewy bodies; Memory; Neurodegeneration; Transgenic mouse