title: Transgenic rodent models to study alpha-synuclein pathogenesis, with a focus on cognitive deficits.
abstract: The aggregation of alpha-synuclein (aSyn) has been implicated in a number of degenerative diseases collectively termed synucleinopathies. Although most cases of synucleinopathies are idiopathic in nature, there are familial cases of these diseases that are due to mutations or multiplications of the gene coding for aSyn. Two of the most common synucleinopathies are Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Both of these diseases present with cognitive deficits, though with different clinical and temporal features. In PD, cognitive deficits are subtle, may occur before the onset of the classical motor symptoms, and only occasionally lead to dementia in the later stages of the disease. In contrast, dementia is the dominating feature of DLB from the disease onset. The impact of aSyn pathology on the development of neurobiological and behavioral impairments can be investigated using rodent models. There are currently several lines of transgenic mice overexpressing wild-type or mutated aSyn under various promoters. This review will provide an updated synopsis of the mouse lines available, summarize their cognitive deficits, and reflect on how deficits observed in these mice relate to the disease process in humans. In addition, we will review mouse lines where knockout strategies have been applied to study the effects of aSyn on various cognitive tasks and comment on how these lines have been used in combination with other transgenic strains, or with human aSyn overexpression by viral vectors. Finally, we will discuss the recent advent of bacterial artificial chromosome (BAC) transgenic models of PD and their effectiveness in modeling cognitive decline in PD.
authors.affiliation: Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, USA, ahatami@mednet.ucla.edu.
authors.forename: Asa
authors.initials: A
authors.lastname: Hatami
authors.forename: Marie-Francoise
authors.initials: MF
authors.lastname: Chesselet
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003072:Cognition Disorders / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein