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The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex
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 (GABA(A)R and GABA(B)R). Alterations in the expression of these signaling compone...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563768/ https://www.ncbi.nlm.nih.gov/pubmed/34728681 http://dx.doi.org/10.1038/s41598-021-00792-8 |
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author | Ethiraj, Jayarjun Palpagama, Thulani Hansika Turner, Clinton van der Werf, Bert Waldvogel, Henry John Faull, Richard Lewis Maxwell Kwakowsky, Andrea |
author_facet | Ethiraj, Jayarjun Palpagama, Thulani Hansika Turner, Clinton van der Werf, Bert Waldvogel, Henry John Faull, Richard Lewis Maxwell Kwakowsky, Andrea |
author_sort | Ethiraj, Jayarjun |
collection | PubMed |
description | 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 (GABA(A)R and GABA(B)R). 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-GABA(A)R α1,2,3,5, β1-3, γ2, GABA(B)R 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 GABA(A)R α1,2,3,5, β1-3, γ2, GABA(B)R 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 GABA(A)R α1subunit level in the CA1 region for females; significant negative correlation between age and GABA(A)R β1, β3 and γ2 subunit expression in the DG region for males. In females a significant positive correlation was found between age and GABA(A)R γ2 subunit expression in the ECx and GABA(B)R 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 GABA(A/B)R subunit alterations in the ECx and hippocampus that might significantly influence GABAergic neurotransmission and underlie disease susceptibility and progression. |
format | Online Article Text |
id | pubmed-8563768 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85637682021-11-04 The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex Ethiraj, Jayarjun Palpagama, Thulani Hansika Turner, Clinton van der Werf, Bert Waldvogel, Henry John Faull, Richard Lewis Maxwell Kwakowsky, Andrea Sci Rep Article 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 (GABA(A)R and GABA(B)R). 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-GABA(A)R α1,2,3,5, β1-3, γ2, GABA(B)R 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 GABA(A)R α1,2,3,5, β1-3, γ2, GABA(B)R 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 GABA(A)R α1subunit level in the CA1 region for females; significant negative correlation between age and GABA(A)R β1, β3 and γ2 subunit expression in the DG region for males. In females a significant positive correlation was found between age and GABA(A)R γ2 subunit expression in the ECx and GABA(B)R 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 GABA(A/B)R subunit alterations in the ECx and hippocampus that might significantly influence GABAergic neurotransmission and underlie disease susceptibility and progression. Nature Publishing Group UK 2021-11-02 /pmc/articles/PMC8563768/ /pubmed/34728681 http://dx.doi.org/10.1038/s41598-021-00792-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ethiraj, Jayarjun Palpagama, Thulani Hansika Turner, Clinton van der Werf, Bert Waldvogel, Henry John Faull, Richard Lewis Maxwell Kwakowsky, Andrea The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex |
title | The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex |
title_full | The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex |
title_fullStr | The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex |
title_full_unstemmed | The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex |
title_short | The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex |
title_sort | effect of age and sex on the expression of gaba signaling components in the human hippocampus and entorhinal cortex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563768/ https://www.ncbi.nlm.nih.gov/pubmed/34728681 http://dx.doi.org/10.1038/s41598-021-00792-8 |
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