Sex- and age-related changes in GABA signaling components in the human cortex
Abstract Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system. Previous studies have shown fluctuations in expression levels of GABA signaling components—glutamic acid decarboxylase (GAD), GABA receptor (GABAR) subunit, and GABA transporter (GAT)—with incre...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Biology of Sex Differences |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13293-018-0214-6 |
| _version_ | 1818063994134462464 |
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| author | Madhavi Pandya Thulani H. Palpagama Clinton Turner Henry J. Waldvogel Richard L. Faull Andrea Kwakowsky |
| author_facet | Madhavi Pandya Thulani H. Palpagama Clinton Turner Henry J. Waldvogel Richard L. Faull Andrea Kwakowsky |
| author_sort | Madhavi Pandya |
| collection | DOAJ |
| description | Abstract Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system. Previous studies have shown fluctuations in expression levels of GABA signaling components—glutamic acid decarboxylase (GAD), GABA receptor (GABAR) subunit, and GABA transporter (GAT)—with increasing age and between sexes; however, this limited knowledge is highly based on animal models that produce inconsistent findings. This study is the first analysis of the age- and sex-specific changes of the GAD, GABAA/BR subunits, and GAT expression in the human primary sensory and motor cortices; superior (STG), middle (MTG), and inferior temporal gyrus (ITG); and cerebellum. Utilizing Western blotting, we found that the GABAergic system is relatively robust against sex and age-related differences in all brain regions examined. However, we observed several sex-dependent differences in GABAAR subunit expression in STG along with age-dependent GABAAR subunit and GAD level alteration. No significant age-related differences were found in α1, α2, α5, β3, and γ2 subunit expression in the STG. However, we found significantly higher GABAAR α3 subunit expression in the STG in young males compared to old males. We observed a significant sex-dependent difference in α1 subunit expression: males presenting significantly higher levels compared to women across all stages of life in STG. Older females showed significantly lower α2, α5, and β3 subunit expression compared to old males in the STG. These changes found in the STG might significantly influence GABAergic neurotransmission and lead to sex- and age-specific disease susceptibility and progression. |
| first_indexed | 2024-12-10T14:28:56Z |
| format | Article |
| id | doaj.art-137fbc50885a45d591a0177aafb03b41 |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-12-10T14:28:56Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-137fbc50885a45d591a0177aafb03b412022-12-22T01:44:59ZengBMCBiology of Sex Differences2042-64102019-01-0110111610.1186/s13293-018-0214-6Sex- and age-related changes in GABA signaling components in the human cortexMadhavi Pandya0Thulani H. Palpagama1Clinton Turner2Henry J. Waldvogel3Richard L. Faull4Andrea Kwakowsky5Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of AucklandCentre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of AucklandCentre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of AucklandCentre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of AucklandCentre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of AucklandCentre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of AucklandAbstract Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system. Previous studies have shown fluctuations in expression levels of GABA signaling components—glutamic acid decarboxylase (GAD), GABA receptor (GABAR) subunit, and GABA transporter (GAT)—with increasing age and between sexes; however, this limited knowledge is highly based on animal models that produce inconsistent findings. This study is the first analysis of the age- and sex-specific changes of the GAD, GABAA/BR subunits, and GAT expression in the human primary sensory and motor cortices; superior (STG), middle (MTG), and inferior temporal gyrus (ITG); and cerebellum. Utilizing Western blotting, we found that the GABAergic system is relatively robust against sex and age-related differences in all brain regions examined. However, we observed several sex-dependent differences in GABAAR subunit expression in STG along with age-dependent GABAAR subunit and GAD level alteration. No significant age-related differences were found in α1, α2, α5, β3, and γ2 subunit expression in the STG. However, we found significantly higher GABAAR α3 subunit expression in the STG in young males compared to old males. We observed a significant sex-dependent difference in α1 subunit expression: males presenting significantly higher levels compared to women across all stages of life in STG. Older females showed significantly lower α2, α5, and β3 subunit expression compared to old males in the STG. These changes found in the STG might significantly influence GABAergic neurotransmission and lead to sex- and age-specific disease susceptibility and progression.http://link.springer.com/article/10.1186/s13293-018-0214-6Sex differenceAgingGADGABAA receptorGABAB receptorGABA transporter |
| spellingShingle | Madhavi Pandya Thulani H. Palpagama Clinton Turner Henry J. Waldvogel Richard L. Faull Andrea Kwakowsky Sex- and age-related changes in GABA signaling components in the human cortex Biology of Sex Differences Sex difference Aging GAD GABAA receptor GABAB receptor GABA transporter |
| title | Sex- and age-related changes in GABA signaling components in the human cortex |
| title_full | Sex- and age-related changes in GABA signaling components in the human cortex |
| title_fullStr | Sex- and age-related changes in GABA signaling components in the human cortex |
| title_full_unstemmed | Sex- and age-related changes in GABA signaling components in the human cortex |
| title_short | Sex- and age-related changes in GABA signaling components in the human cortex |
| title_sort | sex and age related changes in gaba signaling components in the human cortex |
| topic | Sex difference Aging GAD GABAA receptor GABAB receptor GABA transporter |
| url | http://link.springer.com/article/10.1186/s13293-018-0214-6 |
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