Age- and gender-related changes in GABA signalling components in the human cortex

Abstract

GABA signalling components demonstrate high age- and region-specific variability in control and disease cases. The aim of the present study was to investigate the regional and cortical differences in expression of GABA A receptor subunits (α1/2/3/5, β3 & γ2), GABA B receptor subunits (R1 & R2), GABA synthesising enzymes (GAD65 & GAD67) and GABA transporters (GAT1 & GAT3) in healthy human cortex (cerebellum, sensory and motor cortex, superior, middle and inferior temporal gyrus (STG, MTG and ITG, respectively)). The study examined four groups; 6 young females (YF, 51.7 years ± 5.1 years), 6 young males (YM, 47.5 years ± 1.5 years), 6 elderly females (OF, 76 years ± 1.3 years) and 6 elderly males (OM, 80 years ± 1.5 years). Using Western blotting (immunofluorescence based) and immunohistochemistry techniques, GABA signalling components expression patterns were compared between groups. Results showed highest age- and gender-related variability in GABA A receptor subunits in the STG region. Significant age-related decrease in GAT1 expression was seen in cerebellum, sensory cortex and ITG. Motor cortex was well preserved in expression of all components across groups. Overall, the GABAergic system is relatively robust against age- and gender-related differences. In conclusion, this is the first study to characterise expression of GABA signalling components in the cerebellum, temporal gyri and sensory and motor cortex. We identify the regional-, age- and gender-related difference in expression of GABA signalling components in the human brain.