Alcohol Modulation of Extra-synaptic Gamma-aminobutyric Acid Type A Receptors

Arslan, Ayla

doi:10.21533/pen.v4i1.48

Cited by 3 publications

(2 citation statements)

References 75 publications

(98 reference statements)

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“…A small subset of patients with AWS may also experience severe delirium, seizures, and morbidity 3 . The delirium usually begins about 3 days after the appearance of AWS symptoms and lasts between 1 and 8 days (but typically 2 or 3 days) 4–6 . The AWS‐related seizures classically occur between days 2 and 5 of alcohol cessation (12 to 48 h after AWS begins).…”

Section: Introductionmentioning

confidence: 99%

Impact of Traumatic Brain Injury on Clinical Institute Withdrawal Assessment Use in Trauma Patients: A Descriptive Study

Carter

Truong

Šíma

et al. 2020

PM&R

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Background Alcohol withdrawal syndrome (AWS) and traumatic brain injury (TBI) present with similar signs and symptoms, yet their treatment strategies differ greatly. AWS treatment includes the Clinical Institute Withdrawal Assessment (CIWA) protocol, which grades withdrawal signs and symptoms. A major purpose of CIWA is to guide the addition and titration of central nervous system (CNS) depressants, most commonly benzodiazepines. Conversely, best practice is to avoid these same CNS depressants in the setting of TBI. Thus, patients with TBI presenting with AWS risk may receive undesirable interventions that could worsen outcome. Objective To describe the relationship of TBI diagnosis with CIWA protocol scores and intervention implementation. Design Retrospective cohort observational study. Setting Single university‐based, level one trauma center. Patients Three hundred seventy‐five patients with head trauma or AWS classification, identified through the trauma center's trauma registry. Interventions CIWA protocol and related medication use. Main Outcome Measures Frequency of elevated CIWA score, length of CIWA administration, and medication administration incidence were abstracted from patients' medical records. Results The percentage of elevated CIWA scores increased significantly with TBI severity, from 4.5%(0‐60) in the No TBI group, up to 12.5% (0‐36) in the Mild TBI group, 27.1% (0‐57) in the Moderate TBI group, and 50.0% (14‐77) in the Severe TBI group. Nominally, lorazepam use showed a similar pattern of escalation with TBI severity, but it did not reach statistical significance. Haloperidol use did significantly escalate with higher TBI severity. No group differences were observed for total lorazepam equivalents or length on the CIWA protocol. Conclusions TBI diagnosis and higher TBI severity level correlate with higher CIWA scores, but neither increased nor decreased benzodiazepine usage was observed. Antipsychotic use did escalate with TBI diagnosis and severity. The risks versus benefits of minimizing benzodiazepines in patients with TBI who are at risk for AWS warrant future study.

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Section: Introductionmentioning

confidence: 99%

Impact of Traumatic Brain Injury on Clinical Institute Withdrawal Assessment Use in Trauma Patients: A Descriptive Study

Carter

Truong

Šíma

et al. 2020

PM&R

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“…In the cerebellum's granule cells, this subunit shows very strong expression (Wisden et al, 1992). The δ-GABAARs have higher affinity for GABA, neurosteroids as well as for alcohol (Arslan, 2016;Joshi and Kapur, 2019 and mediate slow, tonic inhibition (Farrant and Nusser, 2005;Hausser and Clark, 1997;Semyanov et al, 2004). Tonic inhibition is a special form of inhibition, which is important for the threshold of action potential generation and thus critical for the neural excitability (reviewed in Arslan, 2015a).…”

Section: Introductionmentioning

confidence: 99%

Oligomerization and cell surface expression of recombinant GABAA receptors tagged in the δ subunit

Oflaz

Son

Arslan

2019

J. Integr. Neurosci.

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The γ-Aminobutyric acid type A receptors (GABAARs) are heteropentameric chloride channels responsible for primary inhibition in the mammalian brain. Studies have shown the expression of recombinant GABAAR subunits tagged with the green fluorescent protein (GFP), a 26.9 kDa protein that exhibits bright green fluorescence when exposed to light in the blue to ultraviolet range. This allows the formation of recombinant proteins essential for the development of relevant in-vitro and in-vivo methodologies. Among the GABAAR subunits, the δ subunit was never tagged in its cytoplasmic domain, an evolutionary conserved domain found in between the third and the fourth transmembrane domains. In this study, first, we have cloned the mouse cDNAs encoding for the δ, α1, β2 subunits of GABAARs, and then developed two fusion proteins of δ-subunit each tagged with the GFP variant, EGFP (enhanced GFP) at unique sites in the cytoplasmic domain. The recombinant proteins were expressed alone or in combination with α1 and/or β2 subunits in neuroblastoma 2a cells. Live cell confocal microscopy indicated that the cytoplasmically tagged δ-subunits were targeted to the cell membrane when expressed in the presence of α1 and β2 subunits in neuroblastoma 2a cells. However, this was not observed when they were expressed alone or only with α1 or β2 subunits in the same cell line. These results confirm the general oligomerization and targeting pattern of GABAAR subtypes described in the other in-vitro studies in the literature. Thus, our results suggest that the EGFP tagging in the ctoplasmic domain did not interfere with the oligomerization and cell surface expression of recombinant δ-subunits. To our knowledge, this is the first study showing the generation, expression and preliminary analysis of the δ-GABAARs tagged in the cytoplasmic domain of the δ-subunit which can be further elaborated to probe intracellular protein interactions of GABAARs via the δ-subunit.

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Extrasynaptic δ-subunit containing GABAA receptors

Arslan¹

2021

J. Integr. Neurosci.

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γ-Aminobutyric acid type A receptors (GABAARs) are GABA gated heteropentameric chloride channels responsible for the adult brain’s primary inhibition. In specific brain cells, such as in the hippocampus, one of the subtypes of GABAARs, the δ subunit containing GABAARs (δ-GABAARs), is predominantly expressed and located in extrasynaptic or perisynaptic positions. δ-GABAARs mediate a slow constant inhibitory current called tonic inhibition. While δ-GABAARs and tonic inhibition is critical for the excitability of single neurons, accumulating data suggest that the function of δ-GABAARs are broader and includes an integrative role in the network oscillations. While these open new horizons on the neurobiology of δ-GABAARs, the complexity continues to challenge the analysis of GABAARs and their subtypes. This review will summarize the current knowledge of molecular, cellular and physiological characteristics of δ-GABAARs during health and disease.

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Alcohol Modulation of Extra-synaptic Gamma-aminobutyric Acid Type A Receptors

Cited by 3 publications

References 75 publications

Impact of Traumatic Brain Injury on Clinical Institute Withdrawal Assessment Use in Trauma Patients: A Descriptive Study

Impact of Traumatic Brain Injury on Clinical Institute Withdrawal Assessment Use in Trauma Patients: A Descriptive Study

Oligomerization and cell surface expression of recombinant GABAA receptors tagged in the δ subunit

Extrasynaptic δ-subunit containing GABAA receptors

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