GABAA receptors: building the bridge between subunit mRNAs, their promoters, and cognate transcription factors.
paper
Cited
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- Authors
- Steiger, Janine L; Russek, Shelley J
- Year
- 2004
- Journal
- Pharmacology & therapeutics
- PMID
- 15031002
- DOI
- 10.1016/j.pharmthera.2003.12.002
The type A gamma-aminobutyric acid (GABA(A)) receptors mediate the majority of fast inhibitory neurotransmission in the CNS, and alterations in GABA(A) receptor function is believed to be involved in the pathology of several neurological and psychiatric illnesses, such as epilepsy, anxiety, Alzheimer's disease, and schizophrenia. GABA(A) receptors can be assembled from eight distinct subunit families defined by sequence similarity: alpha(1-6), beta(1-3), gamma(1-3), delta, pi, theta, and rho(1-3). The regulation of GABA(A) receptor function in the brain is a highly compensating system, influencing both the number and the composition of receptors at the cell surface. While transcriptional and translational points of control operate in parallel, it is becoming increasingly evident that many functional changes in GABA(A) receptors reflect the differential gene regulation of its subunits. The fact that certain GABA(A) receptor subunit genes are transcribed in distinct cell types during specific periods of development strongly suggests that genetic control plays a major role in the choice of subunit variants available for receptor assembly. This review focuses on the physiological conditions that alter subunit mRNA levels, the promoters that may control such levels, and the use of a conceptual framework created by bioinformatics to study coordinate and independent GABA(A) receptor subunit gene regulation. As this exciting field moves closer to identifying the language hidden inside the chromatin of GABA(A) receptor subunit gene clusters, future experiments will be aimed at testing models generated by computational analysis with biologically relevant in vivo and in vitro assays. It is hoped that through this functional genomic approach there will be the identification of new targets for therapeutic intervention.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
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| Early developmental changes in GABAA receptor expression in nucleus accumbens medium spiny neurons. | Wang ZZ et al. | β | 2024 | β |
| Impact of Legacy Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoate (PFOA) on GABA Receptor-Mediated Currents in Neuron-Like Neuroblastoma Cells: Insights into Neurotoxic Mechanisms and Health Implications. | Lagostena L et al. | β | 2024 | β |
| Integrated workflow for the identification of new GABA<sub>A</sub> R positive allosteric modulators based on the inβ silico screening with further inβ vitro validation. Case study using Enamine's stock chemical space. | Platonov M et al. | β | 2024 | β |
| Current status of GABA receptor subtypes in analgesia. | Qian X et al. | β | 2023 | β |
| Diazepam-Induced Down-Regulation of the GABA<sub>A</sub> receptor Ξ±1 Subunit, as mediated by the activation of L-Type Voltage-Gated calcium Channel/Ca<sup>2+</sup>/Protein kinase a signaling cascade. | GonzΓ‘lez GΓ³mez LC et al. | β | 2023 | β |
| Gamma-Aminobutyric Acid Type A Receptor Subunit Delta (<i>GABRD</i>) Inhibits Breast Cancer Progression by Regulating the Cell Cycle. | Wu L et al. | β | 2023 | β |
| A missense variant in SHARPIN mediates Alzheimer's disease-specific brain damages. | Park JY et al. | β | 2021 | β |
| Effect of Anti-inflammatory Treatment with AMD3100 and CX<sub>3</sub>CR1 Deficiency on GABA<sub>A</sub> Receptor Subunit and Expression of Glutamate Decarboxylase Isoforms After Stroke. | Michalettos G et al. | β | 2021 | β |
| GABA<sub>A</sub> receptors: structure, function, pharmacology, and related disorders. | Ghit A et al. | β | 2021 | β |
| Regulation of GABA<sub>A</sub> Receptors Induced by the Activation of L-Type Voltage-Gated Calcium Channels. | Gravielle MC | β | 2021 | β |
| Sex-dependent pronociceptive role of spinal Ξ±<sub>5</sub> -GABA<sub>A</sub> receptor and its epigenetic regulation in neuropathic rodents. | Franco-EnzΓ‘stiga Γ et al. | β | 2021 | β |
| Fractional occupancy of synaptic binding sites and the molecular plasticity of inhibitory synapses. | Specht CG | β | 2020 | β |
| GABA<sub>A</sub> Receptor Subunit Transcriptional Regulation, Expression Organization, and Mediated Calmodulin Signaling in Prefrontal Cortex of Rats Showing Testosterone-Mediated Impulsive Behavior. | Agrawal J et al. | β | 2020 | β |
| Induced pluripotent stem cell reprogramming-associated methylation at the GABRA2 promoter and chr4p12 GABA<sub>A</sub> subunit gene expression in the context of alcohol use disorder. | Goetjen A et al. | β | 2020 | β |
| Regulation of GABA<sub>A</sub> Receptor Subunit Expression in Substance Use Disorders. | Barker JS et al. | β | 2020 | β |
| Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells? | Prytkova I et al. | β | 2018 | β |
| PKC/CREB pathway mediates the expressions of GABA<sub>A</sub> receptor subunits in cultured hippocampal neurons after low-Mg<sup>2+</sup> solution treatment. | Wu G et al. | β | 2018 | β |
| Sustained consumption of cocoa-based dark chocolate enhances seizure-like events in the mouse hippocampus. | Cicvaric A et al. | β | 2018 | β |
| GABA<sub>A</sub> Receptors and the Diversity in their Structure and Pharmacology. | Chua HC et al. | β | 2017 | β |
| GABRB2 plays an important role in the lymph node metastasis of papillary thyroid cancer. | Jin Y et al. | β | 2017 | β |
| Ziziphus spinosa seeds for insomnia: A review of chemistry and psychopharmacology. | Shergis JL et al. | β | 2017 | β |
| Diurnal Variation Has Effect on Differential Gene Expression Analysis in the Hippocampus of the Pilocarpine-Induced Model of Mesial Temporal Lobe Epilepsy. | Santos EA et al. | β | 2015 | β |
| GABAergic signalling in the immune system. | Barragan A et al. | β | 2015 | β |
| GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures. | Lieberman R et al. | β | 2015 | β |
| GABRB2 Haplotype Association with Heroin Dependence in Chinese Population. | Kim YS et al. | β | 2015 | β |
| Influence of JuA in evoking communication changes between the small intestines and brain tissues of rats and the GABAA and GABAB receptor transcription levels of hippocampal neurons. | Wang XX et al. | β | 2015 | β |
| In silico inhibition of GABARAP activity using antiepileptic medicinal derived compounds. | Mathew S et al. | β | 2015 | β |
| Bioinformatics analysis of transcriptional regulation of circadian genes in rat liver. | Nguyen TT et al. | β | 2014 | β |
| GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system. | Fritschy JM et al. | β | 2014 | β |
| A factor analysis of global GABAergic gene expression in human brain identifies specificity in response to chronic alcohol and cocaine exposure. | Enoch MA et al. | β | 2013 | β |
| Cholinergic connectivity: it's implications for psychiatric disorders. | Scarr E et al. | β | 2013 | β |
| Identification of the minimal promoter for specific expression of the GABAΟ1 receptor in retinal bipolar cells. | Machuca-Parra AI et al. | β | 2013 | β |
| Isoflurane regulates atypical type-A Ξ³-aminobutyric acid receptors in alveolar type II epithelial cells. | Xiang YY et al. | β | 2013 | β |
| Cholinergic and GABAergic receptor functional deficit in the hippocampus of insulin-induced hypoglycemic and streptozotocin-induced diabetic rats. | Sherin A et al. | β | 2012 | β |
| GABAergic signaling is linked to a hypermigratory phenotype in dendritic cells infected by Toxoplasma gondii. | Fuks JM et al. | β | 2012 | β |
| The protein kinase KIS impacts gene expression during development and fear conditioning in adult mice. | Manceau V et al. | β | 2012 | β |
| Tlx1/3 and Ptf1a control the expression of distinct sets of transmitter and peptide receptor genes in the developing dorsal spinal cord. | Guo Z et al. | β | 2012 | β |
| Effects of inhibitory amino acids on expression of GABAA RΞ± and glycine RΞ±1 in hypoxic rat cortical neurons during development. | Qian H et al. | β | 2011 | β |
| Enhanced GABAergic tone in the ventral pallidum: memory of unpleasant experiences? | Skirzewski M et al. | β | 2011 | β |
| Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer's disease. | Rissman RA et al. | β | 2011 | β |
| Imprinting in the schizophrenia candidate gene GABRB2 encoding GABA(A) receptor Ξ²(2) subunit. | Pun FW et al. | β | 2011 | β |
| Prediction of GABAA receptor proteins using the concept of Chou's pseudo-amino acid composition and support vector machine. | Mohabatkar H et al. | β | 2011 | β |
| Selective Changes of GABA(A) Channel Subunit mRNAs in the Hippocampus and Orbitofrontal Cortex but not in Prefrontal Cortex of Human Alcoholics. | Jin Z et al. | β | 2011 | β |
| Altered Organization of GABA(A) Receptor mRNA Expression in the Depressed Suicide Brain. | Poulter MO et al. | β | 2010 | β |
| Developmental co-regulation of the beta and gamma GABAA receptor subunits with distinct alpha subunits in the human dorsolateral prefrontal cortex. | Fillman SG et al. | β | 2010 | β |
| Effects on the expression of GABAA receptor subunits by jujuboside A treatment in rat hippocampal neurons. | You ZL et al. | β | 2010 | β |
| Influence of 17beta-estradiol and progesterone on GABAergic gene expression in the arcuate nucleus, amygdala and hippocampus of the rhesus macaque. | Noriega NC et al. | β | 2010 | β |
| Regulation of GABA(A) receptor subunit expression by pharmacological agents. | Uusi-Oukari M et al. | β | 2010 | β |
| The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence. | Enoch MA et al. | β | 2010 | β |
| Alteration of epileptogenesis genes. | Brooks-Kayal AR et al. | β | 2009 | β |
| Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. | Hogart A et al. | β | 2009 | β |
| Expression of GABA(A) receptor alpha3-, theta-, and epsilon-subunit mRNAs during rat CNS development and immunolocalization of the epsilon subunit in developing postnatal spinal cord. | Pape JR et al. | β | 2009 | β |
| GABRG1 and GABRA2 as independent predictors for alcoholism in two populations. | Enoch MA et al. | β | 2009 | β |
| The clinical impact of pharmacogenetics on the treatment of epilepsy. | LΓΆscher W et al. | β | 2009 | β |
| Epilepsy, E/I Balance and GABA(A) Receptor Plasticity. | Fritschy JM | β | 2008 | β |
| Expression of the GABA(A) receptor gamma4-subunit gene in discrete nuclei within the zebra finch song system. | Thode C et al. | β | 2008 | β |
| The role of GABA(A) receptors in the development of alcoholism. | Enoch MA | β | 2008 | β |
| Acute hypoxia differentially affects the gamma-aminobutyric acid type A receptor alpha(1), alpha(2), beta(2), and gamma(2) subunit mRNA levels in the developing chick optic tectum: stage-dependent sensitivity. | de Plazas SF et al. | β | 2007 | β |
| Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia. | Newell KA et al. | β | 2007 | β |
| GABA(A) receptors in aging and Alzheimer's disease. | Rissman RA et al. | β | 2007 | β |
| In silico comparative genomic analysis of GABAA receptor transcriptional regulation. | Joyce CJ | β | 2007 | β |
| Positional clustering improves computational binding site detection and identifies novel cis-regulatory sites in mammalian GABAA receptor subunit genes. | Reddy TE et al. | β | 2007 | β |
| [The pharmacology of benzodiazepines]. | BΓΆnisch H | β | 2007 | β |
| Anti-apoptotic effects of allopregnanolone on P19 neurons. | Xilouri M et al. | β | 2006 | β |
| Brain-derived neurotrophic factor (BDNF)-induced synthesis of early growth response factor 3 (Egr3) controls the levels of type A GABA receptor alpha 4 subunits in hippocampal neurons. | Roberts DS et al. | β | 2006 | β |
| Erratum to "Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintenance of epilepsy." [Pharmacol. Ther. 105(3) (2005) 229-266]. | DeLorenzo RJ et al. | β | 2006 | β |
| GABA(A) receptor subtypes as targets for neuropsychiatric drug development. | Korpi ER et al. | β | 2006 | β |
| Modes and models of GABA(A) receptor gating. | Lema GM et al. | β | 2006 | β |
| A common pattern of persistent gene activation in human neocortical epileptic foci. | Rakhade SN et al. | β | 2005 | β |
| Alternative splicing and promoter use in the human GABRA2 gene. | Tian H et al. | β | 2005 | β |
| Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintainance of epilepsy. | Delorenzo RJ et al. | β | 2005 | β |
| Distinct patterns of expression and regulation of GABA receptors containing the delta subunit in cerebellar granule and hippocampal neurons. | Follesa P et al. | β | 2005 | β |
| Egr3 stimulation of GABRA4 promoter activity as a mechanism for seizure-induced up-regulation of GABA(A) receptor alpha4 subunit expression. | Roberts DS et al. | β | 2005 | β |
| Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia. | Petryshen TL et al. | β | 2005 | β |
| Kainic acid-induced status epilepticus alters GABA receptor subunit mRNA and protein expression in the developing rat hippocampus. | LaurΓ©n HB et al. | β | 2005 | β |
| Regulation of dopaminergic transmission and cocaine reward by the Clock gene. | McClung CA et al. | β | 2005 | β |
| The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity. | Hayley S et al. | β | 2005 | β |