GABA transporters GAT-1 and GAT-3 in the human dorsolateral prefrontal cortex in schizophrenia

Neuropsychobiology. 2004;50(3):226-30. doi: 10.1159/000079975.

Abstract

This study aimed to investigate the binding affinity of [3H]GABA and [3H]beta-alanine to GABA transporters GAT-1 and GAT-3 in the human dorsolateral prefrontal cortex (Brodmanns' area 9) in schizophrenia. Using post mortem tissue from individuals diagnosed with schizophrenia (n=6) and control subjects (n=6), the density of GAT-1 was established by displacing [3H]GABA with muscimol, and for GAT-3 [3H]beta-alanine was used. Data analysis showed a significant decrease of GAT-1 levels (45%), and a significant increase of GAT-3 density (23%) within the dorsolateral prefrontal cortex of individuals diagnosed with schizophrenia when compared to age- and sex-matched controls. The observed decrease of GAT-1 could be explained as a consequence of the GABA hypo-function or the result of volumetric shrinkage of the cerebral cortex previously reported in this disease. The observed elevation of GAT-3 levels could be due to a compensatory effect for any functional loss of GABA re-uptake by the decreased GAT-1 levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autopsy
  • Case-Control Studies
  • Female
  • GABA Plasma Membrane Transport Proteins
  • Humans
  • Male
  • Membrane Transport Proteins / analysis*
  • Middle Aged
  • Prefrontal Cortex / physiology*
  • Schizophrenia / physiopathology*
  • beta-Alanine / pharmacokinetics
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacokinetics*

Substances

  • GABA Plasma Membrane Transport Proteins
  • Membrane Transport Proteins
  • SLC6A1 protein, human
  • SLC6A11 protein, human
  • beta-Alanine
  • gamma-Aminobutyric Acid