title: Rescuing the Corticostriatal Synaptic Disconnection in the R6/2 Mouse Model of Huntington's Disease: Exercise, Adenosine Receptors and Ampakines.
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.
authors.affiliation: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.forename: Damian M
authors.initials: DM
authors.lastname: Cummings
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Hickey
authors.forename: Max
authors.initials: M
authors.lastname: Kleiman-Weiner
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Chen
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Watson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine