Extrasynaptic δ-subunit containing GABAA receptors

Arslan, Ayla

doi:10.31083/j.jin.2021.01.284

Cited by 25 publications

(13 citation statements)

References 167 publications

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“…A study by Maguire and Mody ( Maguire and Mody, 2008 ) demonstrated that reduced activation of δ-GABA A Rs has a role in postpartum depression, observing that δ-KO mice have increased depression-like behaviors and an implicit failure in normal maternal behaviors. Brexanolone (allopregnanolone), a neurosteroid agonist which preferentially activates δ-GABA A Rs ( Mihalek et al, 1999 ), has shown efficacy in the treatment of postpartum depression, a condition where endogenous neurosteroids are downregulated in humans ( Ragguett et al, 2019 ; Arslan, 2021 ; Azhar and Din, 2021 ). Rising evidence also suggests that brexanolone could be an effective treatment for other types of mood disorders as well ( Arslan, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Brexanolone (allopregnanolone), a neurosteroid agonist which preferentially activates δ-GABA A Rs ( Mihalek et al, 1999 ), has shown efficacy in the treatment of postpartum depression, a condition where endogenous neurosteroids are downregulated in humans ( Ragguett et al, 2019 ; Arslan, 2021 ; Azhar and Din, 2021 ). Rising evidence also suggests that brexanolone could be an effective treatment for other types of mood disorders as well ( Arslan, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, exogenous neurosteroid analogs that preferentially activate δ-GABA A Rs ( Mihalek et al, 1999 ) have shown efficacy in treatment of postpartum depression ( Ragguett et al, 2019 ; Azhar and Din, 2021 ). More generally, a single nucleotide polymorphism in the GABRD gene (a gene encoding δ-GABA A R subunit) has been observed to affect responses to antidepressant drugs ( Pu et al, 2013 ), and emerging evidence suggests that δ-GABA A Rs are involved in other mental and neurological disorders as well as in induction of drug dependencies ( Arslan, 2021 ). These associations with δ-GABA A Rs and neuropsychiatric disorders make it important to study whether δ-GABA A Rs affect various drug-induced responses.…”

Section: Introductionmentioning

confidence: 99%

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Mice Lacking GABAA Receptor δ Subunit Have Altered Pharmaco-EEG Responses to Multiple Drugs

et al. 2021

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In the brain, extrasynaptically expressed ionotropic, δ subunit-containing γ-aminobutyric acid A-type receptors (δ-GABAARs) have been implicated in drug effects at both neuronal and behavioral levels. These alterations are supposed to be caused via drug-induced modulation of receptor ionophores affecting chloride ion-mediated inhibitory tonic currents. Often, a transgenic mouse model genetically lacking the δ-GABAARs (δ-KO) has been used to study the roles of δ-GABAARs in brain functions, because a specific antagonist of the δ-GABAARs is still lacking. We have previously observed with these δ-KO mice that activation of δ-GABAARs is needed for morphine-induced conditioning of place preference, and others have suggested that δ-GABAARs act as targets selectively for low doses of ethanol. Furthermore, activation of these receptors via drug-mediated agonism induces a robust increase in the slow-wave frequency bands of electroencephalography (EEG). Here, we tested δ-KO mice (compared to littermate wild-type controls) for the pharmaco-EEG responses of a broad spectrum of pharmacologically different drug classes, including alcohol, opioids, stimulants, and psychedelics. Gaboxadol (THIP), a known superagonist of δ-GABAARs, was included as the positive control, and as expected, δ-KO mice produced a blunted pharmaco-EEG response to 6 mg/kg THIP. Pharmaco-EEGs showed notable differences between treatments but also differences between δ-KO mice and their wild-type littermates. Interestingly mephedrone (4-MMC, 5 mg/kg), an amphetamine-like stimulant, had reduced effects in the δ-KO mice. The responses to ethanol (1 g/kg), LSD (0.2 mg/kg), and morphine (20 mg/kg) were similar in δ-KO and wild-type mice. Since stimulants are not known to act on δ-GABAARs, our findings on pharmaco-EEG effects of 4-MMC suggest that δ-GABAARs are involved in the secondary indirect regulation of the brain rhythms after 4-MMC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mice Lacking GABAA Receptor δ Subunit Have Altered Pharmaco-EEG Responses to Multiple Drugs

et al. 2021

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“…45,46 δ-GABAARs mediate a slow constant inhibitory current called tonic inhibition during health and disease. 47 Therefore, at the current stage, the regulatory functions of GABAAR subunits under different expressions are becoming more and more significant in life activities and diseases.…”

Section: Expression and Function Of Gabaar Subunitsmentioning

confidence: 99%

Bibliometric Analysis on GABA-A Receptors Research Based on CiteSpace and VOSviewer

Yu¹,

Gao²,

Gao³

et al. 2023

JPR

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Background: GABA-A receptors are the primary mediators of brain inhibitory neurotransmission. In the past years, many studies focused on this channel to decipher the pathogenesis of related diseases but lacked bibliometric analysis research. This study aims to explore the research status and identify the research trends of GABA-A receptor channels. Methods: Publications related to GABA-A receptor channels were retrieved from the Web of Science Core Collection from 2012 to 2022. After screening, the VOSviewer 1.6.18 and Citespace 5.8 R3 were used for bibliometric analysis from journals, countries, institutions, authors, co-cited references and keywords. Results: We included 12,124 publications in the field of GABA-A receptor channels for analysis. The data shows that although there was a slight decrease in annual publications from 2012 to 2021, it remained at a relatively high level. Most publications were in the domain of neuroscience. Additionally, the United States was the most prolific country, followed by China. Univ Toronto was the most productive institution, and James M Cook led essential findings in this field. Furthermore, brain activation, GABAAR subunits expression, modulation mechanism in pain and anxiety behaviors and GABA and dopamine were paid attention to by researchers. And top research frontiers were molecular docking, autoimmune encephalitic series, obesity, sex difference, diagnosis and management, EEG and KCC2. Conclusion: Taken together, academic attention on GABA-A receptor channels was never neglected since 2012. Our analysis identified key information, such as core countries, institutions and authors in this field. Molecular docking, autoimmune encephalitic series, obesity, sex difference, diagnosis and management, EEG and KCC2 will be the future research direction.

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“…Gamma-aminobutyric acid type A receptor subunit delta (GABRD) is a ligand-gated ion channel-type receptor that has been linked to a wide range of neurological and psychiatric disease-related symptoms as well as the progression of cancer [ 25 ]. Recent research has shed light on the potential functional functions that GABRD played in the development of malignancies.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of the Expression, Prognostic Value, and Immune Infiltration Activities of GABRD in Colon Adenocarcinoma

Huang

Wang

Zhu

et al. 2023

Mediators of Inflammation

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Colon adenocarcinoma (COAD) is one of the tumors with the highest mortality rates. It is of the utmost significance to make an accurate prognostic assessment and to tailor one’s treatment to the specific needs of the patient. Multiple lines of evidence point to the possibility that genetic variables and clinicopathological traits are connected to the onset and development of cancer. In the past, a number of studies have revealed that gamma-aminobutyric acid type A receptor subunit delta (GABRD) plays a role in the advancement of a number of different cancers. However, its function in COAD was rarely reported. In this study, we analyzed TCGA datasets and identified 29 survival-related differentially expressed genes (DEGs) in COAD patients. In particular, GABRD expression was noticeably elevated in COAD specimens. There was a correlation between high GABRD expression and an advanced clinical stage. According to the results of the survival tests, patients whose GABRD expression was high had a lower overall survival time and progression-free survival time than those whose GABRD expression was low. GABRD expression was found to be an independent predictive predictor for overall survival, as determined by multivariate COX regression analysis. Additionally, the predictive nomogram model can accurately predict the fate of individuals with COAD. In addition, we observed that GABRD expressions were positively associated with the expression of T cells regulatory (Tregs), macrophages M0, while negatively associated with the expression of T cells CD8, T cells follicular helper, macrophages M1, dendritic cells activated, eosinophils, and T cells CD4 memory activated. The IC50 of BI-2536, bleomycin, embelin, FR-180204, GW843682X, LY317615, NSC-207895, rTRAIL, and VX-11e was higher in the GABRD high-expression group. In conclusion, we have shown evidence that GABRD is a novel biomarker that is connected with immune cell infiltration in COAD and may be utilized to predict the prognosis of COAD patients.

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Extrasynaptic δ-subunit containing GABAA receptors

Cited by 25 publications

References 167 publications

Mice Lacking GABAA Receptor δ Subunit Have Altered Pharmaco-EEG Responses to Multiple Drugs

Mice Lacking GABAA Receptor δ Subunit Have Altered Pharmaco-EEG Responses to Multiple Drugs

Bibliometric Analysis on GABA-A Receptors Research Based on CiteSpace and VOSviewer

Comprehensive Analysis of the Expression, Prognostic Value, and Immune Infiltration Activities of GABRD in Colon Adenocarcinoma

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