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

Cell Stem Cell. 2012 Apr 6;10(4):455-64. doi: 10.1016/j.stem.2012.01.021. Epub 2012 Mar 15.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cell Transplantation / methods
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / biosynthesis
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • GABAergic Neurons / cytology
  • GABAergic Neurons / metabolism*
  • GABAergic Neurons / transplantation*
  • Gait Disorders, Neurologic / chemically induced
  • Gait Disorders, Neurologic / metabolism
  • Gait Disorders, Neurologic / therapy*
  • Gene Expression Regulation
  • Humans
  • Mice
  • Prosencephalon / metabolism*
  • Quinolinic Acid / toxicity*
  • Substantia Nigra / metabolism
  • Transplantation, Heterologous


  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • PPP1R1B protein, human
  • Quinolinic Acid