Age-correlated decline in [3H]tiagabine binding to GAT-1 in human frontal cortex.
OBJECTIVE
In spite of the fact that GABA is a significant transmitter, little is known about the GABA system in aging, compared with other transmitter systems. [(3)H]tiagabine is a ligand for GABAergic neurons, which binds with 10-fold higher affinity to the GABA uptake site than [(3)H]nipecotic acid. The aim of this study was to study the binding of [(3)H]tiagabine to the GABA transporter 1, GAT-1, in human frontal cortex and cingulate cortex from individuals of varying ages.


METHODS
[(3)H]tiagabine binding experiments were conducted on post-mortem brain tissue from 19 individuals (age range 17-78 years) without known neurological or psychiatric disorders. Binding data vs age and postmortem interval was analysed by Pearson correlation.


RESULTS
The density of [(3)H]tiagabine binding to GAT- 1 decreased significantly with increasing age in the frontal cortex, whereas binding affinity was unchanged. No significant alterations in binding parameters were observed in the cingulate cortex. No correlation was found between post-mortem delay and the number of [(3)H]tiagabine binding sites.


CONCLUSIONS
According to the present study, presynaptical alterations in the GABA system are correlated with aging in the frontal cortex of the human brain. Further studies involving a broader range of brain regions seem warranted, to confirm the present findings and to enlarge knowledge about the GABA system in aging.
Sundman-Eriksson
Ingrid
I
Department of Clinical Sciences, Division of Psychiatry, Umeå University, 901 85 Umeå, Sweden.
Allard
Per
P
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001665:Binding Sites; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D000078308:Tiagabine; D014316:Tritium
D050485:GABA Plasma Membrane Transport Proteins; D009557:Nipecotic Acids; D014316:Tritium; D000078308:Tiagabine