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Rescuing the Corticostriatal Synaptic Disconnection in the R6/2 Mouse Model of Huntington's Disease: Exercise, Adenosine Receptors and Ampakines.

Cepeda, C; Cummings, DM; Hickey, MA; Kleiman-Weiner, M; Chen, JY; Watson, JB; Levine, MS; (2010) Rescuing the Corticostriatal Synaptic Disconnection in the R6/2 Mouse Model of Huntington's Disease: Exercise, Adenosine Receptors and Ampakines. PLoS Currents Huntington Disease , 2 10.1371/currents.RRN1182. Green open access

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Abstract

In the R6/2 mouse model of Huntington's disease (HD) we examined the effects of a number of behavioral and pharmacological manipulations aimed at rescuing the progressive loss of synaptic communication between cerebral cortex and striatum. Two cohorts of transgenic mice with ~110 and 210 CAG repeats were utilized. Exercise prevented the reduction in striatal medium-sized spiny neuron membrane capacitance but did not reestablish synaptic communication. Activation of adenosine A2A type receptors renormalized postsynaptic activity to some extent. Finally, the ampakine Cx614, which has been shown to prevent α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor desensitization, slow deactivation, and facilitate glutamate release, induced significant increases in synaptic activity, albeit the effect was somewhat reduced in fully symptomatic, compared to control mice. With some limitations, each of these strategies can be used to delay and partially rescue phenotypic progression of HD in this model.

Type: Article
Title: Rescuing the Corticostriatal Synaptic Disconnection in the R6/2 Mouse Model of Huntington's Disease: Exercise, Adenosine Receptors and Ampakines.
Location: US
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/currents.RRN1182
Publisher version: http://dx.doi.org/10.1371/currents.RRN1182
Language: English
Additional information: © 2010 Cepeda et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC2945295
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1338624
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