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Media type:
E-Article
Title:
Restoring GABAergic inhibition rescues memory deficits in a Huntington’s disease mouse model
Contributor:
Dargaei, Zahra;
Bang, Jee Yoon;
Mahadevan, Vivek;
Khademullah, C. Sahara;
Bedard, Simon;
Parfitt, Gustavo Morrone;
Kim, Jun Chul;
Woodin, Melanie A.
Published:
Proceedings of the National Academy of Sciences, 2018
Published in:
Proceedings of the National Academy of Sciences, 115 (2018) 7
Language:
English
DOI:
10.1073/pnas.1716871115
ISSN:
1091-6490;
0027-8424
Origination:
Footnote:
Description:
SignificanceHuntington’s disease (HD) is a fatal neurodegenerative disorder that currently has no cure. Although HD is classically considered a motor disorder, HD patients experience learning and memory deficits years before the onset of motor symptoms, and these deficits resemble those observed in HD mouse models. In this work, using transgenic mouse models of HD, we demonstrate that the action of the neurotransmitter GABA has switched from inhibitory to excitatory. By treating HD mice with a clinically used diuretic (bumetanide), which restores inhibitory GABA, we rescued the learning and memory deficits. Our data suggest a potential therapeutic approach for the treatment of the cognitive deficits in early HD that can improve patient quality of life and reduce caregiver burden.