GABA transporters GAT-1 and GAT-3 in the human dorsolateral prefrontal cortex in schizophrenia.
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.
Schleimer
Sonja B
SB
Department of Pharmacology & Neuroscience Institute of Schizophrenia and Allied Disorders, Sydney, Australia. sonny@med.usyd.edu.au
Hinton
Tina
T
Dixon
Gavin
G
Johnston
Graham A R
GA
D000328:Adult; D001344:Autopsy; D016022:Case-Control Studies; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis*; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology*; D012559:Schizophrenia / Q000503:physiopathology*; D015091:beta-Alanine / Q000493:pharmacokinetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000493:pharmacokinetics*
D050485:GABA Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; C493413:SLC6A1 protein, human; C493416:SLC6A11 protein, human; D015091:beta-Alanine; D005680:gamma-Aminobutyric Acid