The contribution of GABAergic dysfunction to neurodevelopmental disorders

Trends Mol Med. 2011 Aug;17(8):452-62. doi: 10.1016/j.molmed.2011.03.003. Epub 2011 Apr 21.

Abstract

GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the brain. The GABAergic system is indispensable for maintaining the balance between excitation and inhibition (E/I balance) required for normal neural circuit function. E/I imbalances that result from perturbations in the development of this system, ranging from the generation of inhibitory neurons to the formation of their synaptic connections, have been implicated in several neurodevelopmental disorders. In this review, we discuss how impairments at different stages in GABAergic development can lead to disease states. We also highlight recent studies which show that modulation of the GABAergic system can successfully reverse cognitive deficits in disease models and suggest that therapeutic strategies targeting the GABAergic system could be effective in treating neurodevelopmental disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Gene Expression Regulation
  • Humans
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / physiopathology*
  • Neurons / metabolism*
  • Neurons / pathology
  • Synapses / metabolism
  • gamma-Aminobutyric Acid / physiology*

Substances

  • gamma-Aminobutyric Acid