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Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice.

ABSTRACT: Degeneration of medium spiny GABA neurons in the basal ganglia underlies motor dysfunction in Huntington's disease (HD), which presently lacks effective therapy. In this study, we have successfully directed human embryonic stem cells (hESCs) to enriched populations of DARPP32-expressing forebrain GABA neurons. Transplantation of these human forebrain GABA neurons and their progenitors, but not spinal GABA cells, into the striatum of quinolinic acid-lesioned mice results in generation of large populations of DARPP32(+) GABA neurons, which project to the substantia nigra as well as receiving glutamatergic and dopaminergic inputs, corresponding to correction of motor deficits. This finding raises hopes for cell therapy for HD.

SUBMITTER: Ma L

PROVIDER: S-EPMC3322292 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice.

Ma Lixiang L Hu Baoyang B Liu Yan Y Vermilyea Scott Christopher SC Liu Huisheng H Gao Lu L Sun Yan Y Zhang Xiaoqing X Zhang Su-Chun SC

Cell stem cell 20120315 4

Degeneration of medium spiny GABA neurons in the basal ganglia underlies motor dysfunction in Huntington's disease (HD), which presently lacks effective therapy. In this study, we have successfully directed human embryonic stem cells (hESCs) to enriched populations of DARPP32-expressing forebrain GABA neurons. Transplantation of these human forebrain GABA neurons and their progenitors, but not spinal GABA cells, into the striatum of quinolinic acid-lesioned mice results in generation of large po ...[more]

PMID: 22424902

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