Alteration of GABAergic neurotransmission in Huntington’s disease

Maurice Garret, Zhuowei Du, Marine Chazalon, Yoon H. Cho, Jérôme Baufreton
CNS Neurosci Ther. 2018-02-21; 24(4): 292-300
DOI: 10.1111/cns.12826

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1. CNS Neurosci Ther. 2018 Apr;24(4):292-300. doi: 10.1111/cns.12826. Epub 2018 Feb

Alteration of GABAergic neurotransmission in Huntington’s disease.

Garret M(1)(2), Du Z(1)(2), Chazalon M(3)(4), Cho YH(1)(2), Baufreton J(3)(4).

Author information:
(1)Université de Bordeaux, INCIA, UMR 5287, Bordeaux, France.
(2)CNRS, INCIA, UMR 5287, Bordeaux, France.
(3)Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293,
Bordeaux, France.
(4)Institut des Maladies Neurodégénératives, CNRS, UMR 5293, Bordeaux, France.

Hereditary Huntington’s disease (HD) is characterized by cell dysfunction and
death in the brain, leading to progressive cognitive, psychiatric, and motor
impairments. Despite molecular and cellular descriptions of the effects of the HD
mutation, no effective pharmacological treatment is yet available. In addition to
well-established alterations of glutamatergic and dopaminergic neurotransmitter
systems, it is becoming clear that the GABAergic systems are also impaired in HD.
GABA is the major inhibitory neurotransmitter in the brain, and GABAergic
neurotransmission has been postulated to be modified in many neurological and
psychiatric diseases. In addition, GABAergic neurotransmission is the target of
many drugs that are in wide clinical use. Here, we summarize data demonstrating
the occurrence of alterations of GABAergic markers in the brain of HD carriers as
well as in rodent models of the disease. In particular, we pinpoint HD-related
changes in the expression of GABAA receptors (GABAA Rs). On the basis that a
novel GABA pharmacology of GABAA Rs established with more selective drugs is
emerging, we argue that clinical treatments acting specifically on GABAergic
neurotransmission may be an appropriate strategy for improving symptoms linked to
the HD mutation.

© 2018 John Wiley & Sons Ltd.

DOI: 10.1111/cns.12826
PMID: 29464851

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