GABA is the primary inhibitory neurotransmitter in the adult brain and through its actions on GABARs, it protects against excitotoxicity and seizure activity, ensures temporal fidelity of neurotransmission, and regulates concerted rhythmic activity of neuronal populations. In the developing brain, the development of GABAergic neurons precedes that of glutamatergic neurons and the GABA system serves as a guide and framework for the development of other brain systems. Despite this early start, the maturation of the GABA system also continues well into the early postnatal period. In this review, we organize evidence around two scenarios based on the essential and protracted nature of GABA system development: 1) disruptions in the development of the GABA system can lead to large scale disruptions in other developmental processes (i.e., GABA as the cause), 2) protracted maturation of this system makes it vulnerable to the effects of developmental insults (i.e., GABA as the effect). While ample evidence supports the importance of GABA/GABAR system in both scenarios, large gaps in existing knowledge prevent strong mechanistic conclusions.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11081854 | PMC |
http://dx.doi.org/10.1016/j.neubiorev.2024.105651 | DOI Listing |
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.
View Article and Find Full Text PDFIBRO Neurosci Rep
December 2024
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Previous investigations have revealed the role of GABAergic and serotonergic systems in the modulation of pain behavior. This research aimed to examine the effects of intracerebroventricular (i.c.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
January 2025
Department of Pharmacology, Catholic Kwandong University College of Medicine, Gangneung 25601, Korea.
Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl- D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors.
View Article and Find Full Text PDFAlzheimers Res Ther
January 2025
Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
Background: The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitter system plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Riluzole is a Glu modulator originally approved for amyotrophic lateral sclerosis that has shown potential neuroprotective effects in various neurodegenerative disorders. However, whether riluzole can improve Glu and GABA homeostasis in AD brain and its related mechanism of action remain unknown.
View Article and Find Full Text PDFCiprofol, a novel γ-aminobutyric acid receptor agonist, outperforms propofol with minimal cardiovascular effects, higher potency, reduced injection pain, and a broader safety margin. Despite these advantages, ciprofol's clinical research is still emerging. This study compares the median effective dose (ED) and adverse reactions of ciprofol and propofol, in conjunction with sufentanil, for suppressing cardiovascular responses during tracheal intubation.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!