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Special Issue "GABAergic Physiology in Neurological Disorders"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 29 September 2021.

Special Issue Editor

Dr. Ciria C. Hernandez
E-Mail Website
Guest Editor
University of Michigan, Ann Arbor, United States
Interests: voltage and ligand gated ion channel structure and function; channelopathies; signaling transduction; G-protein coupled receptors structure and function; epilepsy and metabolism; variants and pathogenic mutations

Special Issue Information

Dear Colleagues,

In this era, our knowledge of GABAergic function has advanced beyond the description that GABAA receptors are composed of 19 different subunit subtypes (α1–α6, β1–β3, γ1–γ3, δ, ɛ, π, θ, and ρ1–ρ3). Rather, we add to this the complexity that these subunits differentially express at certain sites in the brain where unique signaling pathways are formed, and meticulously regulate neurological excitability in epileptic and metabolic circuits. So far, hundreds of variants, monogenic mutations, and de novo mutations in the classical α, β, and γ GABAA receptors subunits have been described in moderate to severe neurological disorders, in which GABAergic signaling seems compromised in tuning the inhibition of key circuits that maintain homeostasis of neuronal excitability. However, even more, latter transcriptomics studies of specific neuronal groups in less studied physiological states, such as the pathways that regulate energy homeostasis, have revealed the emergence of less conventional GABAA receptor subunits that govern neuronal tonic inhibition at these sites. These observations paint a complex picture for the physiology of GABAA receptors in the brain, where we cannot simply consider or isolate the contribution of a single type or class of receptor to a single type or class of circuit, or to a single type or kind of disorder or pathology.

The scope of the Special Issue is to bring together original research and review articles on GABAergic signaling on physiological and pathological conditions, thus summarizing and expanding our knowledge on signaling processes and networks in a variety of neurons in the brain. Highlighting new methodologies that will ultimately advance our understanding of the current state of cellular signaling processes in which GABA is involved.

Topics include but are not limited to:

  • GABAA receptor physiology and pharmacology
  • GABAergic modulation of the excitatory/inhibitory balance in the brain
  • GABAergic signaling in developmental epileptic encephalopathies
  • GABAergic signaling in inherited epilepsies
  • GABAergic signaling in normal regulation of energy balance
  • GABAergic signaling in metabolic disorders
  • Therapeutic perspectives of GABAergic signaling

Dr. Ciria C. Hernandez
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • GABAA receptors
  • Inhibitory/excitatory balance
  • GABAergic circuitry
  • Epilepsy
  • Energy balance
  • Pharmacology
  • Drug discovery
  • Neurological disorders
  • De novo mutations

Published Papers (2 papers)

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Review

Open AccessReview
The Role of Phospholipase C in GABAergic Inhibition and Its Relevance to Epilepsy
Int. J. Mol. Sci. 2021, 22(6), 3149; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063149 - 19 Mar 2021
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Abstract
Epilepsy is characterized by recurrent seizures due to abnormal hyperexcitation of neurons. Recent studies have suggested that the imbalance of excitation and inhibition (E/I) in the central nervous system is closely implicated in the etiology of epilepsy. In the brain, GABA is a [...] Read more.
Epilepsy is characterized by recurrent seizures due to abnormal hyperexcitation of neurons. Recent studies have suggested that the imbalance of excitation and inhibition (E/I) in the central nervous system is closely implicated in the etiology of epilepsy. In the brain, GABA is a major inhibitory neurotransmitter and plays a pivotal role in maintaining E/I balance. As such, altered GABAergic inhibition can lead to severe E/I imbalance, consequently resulting in excessive and hypersynchronous neuronal activity as in epilepsy. Phospholipase C (PLC) is a key enzyme in the intracellular signaling pathway and regulates various neuronal functions including neuronal development, synaptic transmission, and plasticity in the brain. Accumulating evidence suggests that neuronal PLC is critically involved in multiple aspects of GABAergic functions. Therefore, a better understanding of mechanisms by which neuronal PLC regulates GABAergic inhibition is necessary for revealing an unrecognized linkage between PLC and epilepsy and developing more effective treatments for epilepsy. Here we review the function of PLC in GABAergic inhibition in the brain and discuss a pathophysiological relationship between PLC and epilepsy. Full article
(This article belongs to the Special Issue GABAergic Physiology in Neurological Disorders)
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Open AccessReview
Intricacies of GABAA Receptor Function: The Critical Role of the β3 Subunit in Norm and Pathology
Int. J. Mol. Sci. 2021, 22(3), 1457; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031457 - 01 Feb 2021
Viewed by 601
Abstract
Neuronal intracellular chloride ([Cl]i) is a key determinant in γ-aminobutyric acid type A (GABA)ergic signaling. γ-Aminobutyric acid type A receptors (GABAARs) mediate both inhibitory and excitatory neurotransmission, as the passive fluxes of Cl and HCO3 [...] Read more.
Neuronal intracellular chloride ([Cl]i) is a key determinant in γ-aminobutyric acid type A (GABA)ergic signaling. γ-Aminobutyric acid type A receptors (GABAARs) mediate both inhibitory and excitatory neurotransmission, as the passive fluxes of Cl and HCO3 via pores can be reversed by changes in the transmembrane concentration gradient of Cl. The cation–chloride co-transporters (CCCs) are the primary systems for maintaining [Cl]i homeostasis. However, despite extensive electrophysiological data obtained in vitro that are supported by a wide range of molecular biological studies on the expression patterns and properties of CCCs, the presence of ontogenetic changes in [Cl]i—along with the consequent shift in GABA reversal potential—remain a subject of debate. Recent studies showed that the β3 subunit possesses properties of the P-type ATPase that participates in the ATP-consuming movement of Cl via the receptor. Moreover, row studies have demonstrated that the β3 subunit is a key player in GABAAR performance and in the appearance of serious neurological disorders. In this review, we discuss the properties and driving forces of CCCs and Cl, HCO3ATPase in the maintenance of [Cl]i homeostasis after changes in upcoming GABAAR function. Moreover, we discuss the contribution of the β3 subunit in the manifestation of epilepsy, autism, and other syndromes. Full article
(This article belongs to the Special Issue GABAergic Physiology in Neurological Disorders)
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