Abstract
Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system. The GABA signaling system in the brain is comprised of GABA synthesizing enzymes, transporters, GABAA and GABAB receptors (GABAAR and GABABR). Alterations in the expression of these signaling components have been observed in several brain regions throughout aging and between sexes in various animal models. The hippocampus is the memory centre of the brain and is impaired in several age-related disorders. It is composed of two main regions: the Cornu Ammonis (CA1-4) and the Dentate Gyrus (DG), which are interconnected with the Entorhinal Cortex (ECx). The age- and sex-specific changes of GABA signaling components in these regions of the human brain have not been examined. This study is the first to determine the effect of age and sex on the expression of GABA signaling components-GABAAR α1,2,3,5, β1-3, γ2, GABABR R1 and R2 subunits and the GABA synthesizing enzymes GAD 65/67-in the ECx, and the CA1 and DG regions of the human hippocampus using Western blotting. No significant differences were found in GABAAR α1,2,3,5, β1-3, γ2, GABABR R1 and R2 subunit and GAD65/76 expression levels in the ECx, CA1 and DG regions between the younger and older age groups for both sexes. However, we observed a significant negative correlation between age and GABAAR α1subunit level in the CA1 region for females; significant negative correlation between age and GABAAR β1, β3 and γ2 subunit expression in the DG region for males. In females a significant positive correlation was found between age and GABAAR γ2 subunit expression in the ECx and GABABR R2 subunit expression in the CA1 region. The results indicate that age and sex do not affect the expression of GAD 65/67. In conclusion, our results show age- and sex-related GABAA/BR subunit alterations in the ECx and hippocampus that might significantly influence GABAergic neurotransmission and underlie disease susceptibility and progression.
Highlights
Gamma-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian brain
We showed a significant age-related decrease in G ABAAR α3 subunit expression in the human superior temporal gyrus (STG) of males, there were no changes in other cortical areas such as the primary sensory and motor cortices, medial temporal gyrus (MTG), inferior temporal gyrus (ITG) and cerebellum[6]
There is conflicting evidence, with a recent paper showing no significant changes in levels of GABAAR subunits in the mouse[11], previous studies have shown an age-related increase in the expression of α1 and γ2 subunits in the rat h ippocampus[12,13,14]
Summary
Gamma-aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian brain. There is conflicting evidence, with a recent paper showing no significant changes in levels of GABAAR subunits in the mouse[11], previous studies have shown an age-related increase in the expression of α1 and γ2 subunits in the rat h ippocampus[12,13,14]. Hippocampal GTP-binding was comparable between young and aged rats but reduced hippocampal G ABAB R1 expression was observed in aged rats with spatial learning impairment, indicating that normal aging differentially modulates the expression of GABABRs between the PFC and hippocampus and these changes have significant effects on signaling efficacy within the PFC but not in the h ippocampus[19]. Another study reports reduced GABAB R1 and R2 subunit expression with age in the rat PFC that is associated with increased performance in working memory tests[21]. The current data suggests that the age-related changes in GABABR expression is complex and the functional implications are still not fully understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
