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Deletion of alpha-synuclein decreases impulsivity in mice

Peña-Oliver, Y., Buchman, Vladimir L., Dalley, J. W., Robbins, T. W., Schumann, G., Ripley, T. L., King, S. L. and Stephens, D. N. 2012. Deletion of alpha-synuclein decreases impulsivity in mice. Genes, Brain and Behavior 11 (2) , pp. 137-146. 10.1111/j.1601-183X.2011.00758.x

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Abstract

The presynaptic protein alpha-synuclein, associated with Parkinson's Disease (PD), plays a role in dopaminergic neurotransmission and is implicated in impulse control disorders (ICDs) such as drug addiction. In this study we investigated a potential causal relationship between alpha-synuclein and impulsivity, by evaluating differences in motor impulsivity in the 5-choice serial reaction time task (5-CSRTT) in strains of mice that differ in the expression of the alpha-synuclein gene. C57BL/6JOlaHsd mice differ from their C57BL/6J ancestors in possessing a chromosomal deletion resulting in the loss of two genes, snca, encoding alpha-synuclein, and mmrn1, encoding multimerin-1. C57BL/6J mice displayed higher impulsivity (more premature responding) than C57BL/6JOlaHsd mice when the pre-stimulus waiting interval was increased in the 5-CSRTT. In order to ensure that the reduced impulsivity was indeed related to snca, and not adjacent gene deletion, wild type (WT) and mice with targeted deletion of alpha-synuclein (KO) were tested in the 5-CSRTT. Similarly, WT mice were more impulsive than mice with targeted deletion of alpha-synuclein. Interrogation of our ongoing analysis of impulsivity in BXD recombinant inbred mouse lines revealed an association of impulsive responding with levels of alpha-synuclein expression in hippocampus. Expression of beta- and gamma-synuclein, members of the synuclein family that may substitute for alpha-synuclein following its deletion, revealed no differential compensations among the mouse strains. These findings suggest that alpha-synuclein may contribute to impulsivity and potentially, to ICDs which arise in some PD patients treated with dopaminergic medication.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QR Microbiology
Uncontrolled Keywords: Alpha-synuclein; impulse control disorders; impulsivity; Parkinson's disease
Publisher: Wiley-Blackwell
ISSN: 1601-1848
Last Modified: 04 Jun 2017 06:49
URI: http://orca.cf.ac.uk/id/eprint/65095

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