Early GABAergic transmission defects in the external globus pallidus and rest/activity rhythm alteration in a mouse model of Huntington’s disease.

Zhuowei Du, Marine Chazalon, Emma Bestaven, Thierry Leste-Lasserre, Jérôme Baufreton, Jean-René Cazalets, Yoon H. Cho, Maurice Garret
Neuroscience. 2016-08-01; 329: 363-379
DOI: 10.1016/j.neuroscience.2016.05.027

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1. Neuroscience. 2016 Aug 4;329:363-79. doi: 10.1016/j.neuroscience.2016.05.027.
Epub 2016 May 20.

Early GABAergic transmission defects in the external globus pallidus and
rest/activity rhythm alteration in a mouse model of Huntington’s disease.

Du Z(1), Chazalon M(2), Bestaven E(1), Leste-Lasserre T(3), Baufreton J(2),
Cazalets JR(1), Cho YH(1), Garret M(4).

Author information:
(1)Univ. Bordeaux, INCIA, UMR 5287, F-33000 Bordeaux, France; CNRS, INCIA, UMR
5287, F-33000 Bordeaux, France.
(2)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France.
(3)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U862, F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie,
Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
(4)Univ. Bordeaux, INCIA, UMR 5287, F-33000 Bordeaux, France; CNRS, INCIA, UMR
5287, F-33000 Bordeaux, France. Electronic address: .

Huntington’s disease (HD) is characterized by progressive motor symptoms preceded
by cognitive deficits and is regarded as a disorder that primarily affects the
basal ganglia. The external globus pallidus (GPe) has a central role in the basal
ganglia, projects directly to the cortex, and is majorly modulated by GABA. To
gain a better understanding of the time course of HD progression and gain insight
into the underlying mechanisms, we analyzed GABAergic neurotransmission in the
GPe of the R6/1 mouse model at purportedly asymptomatic and symptomatic stages
(i.e., 2 and 6months). Western blot and quantitative polymerase chain reaction
(PCR) analyses revealed alterations in the GPe of male R6/1 mice compared with
wild-type littermates. Expression of proteins involved in pre- and post-synaptic
GABAergic compartments as well as synapse number were severely decreased at 2 and
6months. At both ages, patch-clamp electrophysiological recordings showed a
decrease of spontaneous and miniature inhibitory post-synaptic currents (IPSCs)
suggesting that HD mutation has an early effect on the GABA signaling in the
brain. Therefore, we performed continuous locomotor activity recordings from 2 to
4months of age. Actigraphy analyses revealed rest/activity fragmentation
alterations that parallel GABAergic system impairment at 2months, while the
locomotor deficit is evident only at 3months in R6/1 mice. Our results reveal
early deficits in HD and support growing evidence for a critical role played by
the GPe in physiological and pathophysiological states. We suggest that actimetry
may be used as a non-invasive tool to monitor early disease progression.

Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.neuroscience.2016.05.027
PMID: 27217211 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus