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| http://dx.doi.org/10.1038/s41386-021-01142-y | DOI Listing |
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The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABA receptors under ischemic conditions by inhibiting fast receptor recycling.
Sci Rep
January 2025
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
GABA receptors mediate prolonged inhibition in the brain and are important for keeping neuronal excitation and inhibition in a healthy balance. However, under excitotoxic/ischemic conditions, GABA receptors are downregulated by dysregulated endocytic trafficking and can no longer counteract the severely enhanced excitation, eventually triggering neuronal death. Recently, we developed interfering peptides targeting protein-protein interactions involved in downregulating the receptors.
View Article and Find Full Text PDFInfantile Spasms in Pediatric Down Syndrome: Potential Mechanisms Driving Therapeutic Considerations.
Children (Basel)
December 2024
Division of Pediatric Neurology, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Infantile spasms are common in Down Syndrome (DS), but the mechanisms by which DS predisposes to this devastating epilepsy syndrome are unclear. In general, neuronal excitability and therefore seizure predisposition results from an imbalance of excitation over inhibition in neurons and neural networks of the brain. Animal models provide clues to mechanisms and thereby provide potential therapeutic approaches.
View Article and Find Full Text PDFMetabotropic GABA Receptor Activation Induced by G Protein Coupling.
J Am Chem Soc
January 2025
Materials and Process Simulation Center, California Institute of Technology, Pasadena, California 91125, United States.
G protein-coupled receptors (GPCRs) play central roles in regulating cellular responses through heterotrimeric G proteins (GP). Extensive studies have elucidated the complex cellular signaling mediated by GPCRs that accompany dynamic conformational changes upon activation. However, there has been less focus on the role of the GP on the activation process, particularly for class C GPCRs that function as obligate dimers.
View Article and Find Full Text PDFEstrogen-regulated lateral septal kisspeptin neurons abundantly project to GnRH neurons and the hypothalamic supramammillary nucleus.
J Neurosci
January 2025
Laboratory of Reproductive Neurobiology, Hun-Ren Institute of Experimental Medicine, Budapest, 1083 Hungary;
While hypothalamic kisspeptin (KP) neurons play well-established roles in the estrogen-dependent regulation of reproduction, little is known about extrahypothalamic KP-producing (KP) neurons of the lateral septum. As established previously, expression in this region is low and regulated by estrogen receptor- and GABA receptor-dependent mechanisms. Our present experiments on knock-in mice revealed that transgene expression in the LS begins at P33-36 in females and P40-45 in males and is stimulated by estrogen receptor signaling.
View Article and Find Full Text PDFAn α7 nicotinic and GABA receptor-mediated pathway controls acetylcholine release in the tripartite neuromuscular junction.
J Physiol
December 2024
Université Paris Cité, CNRS, ENS Paris Saclay, Centre Borelli UMR 9010, Paris, France.
Terminal Schwann cells (TSCs) are capable of regulating acetylcholine (ACh) release at the neuromuscular junction (NMJ). We have identified GABA as a gliotransmitter at mouse NMJs. When ACh activates α7 nicotinic ACh receptor (nAChRs) on TSCs, GABA is released and activates GABA receptors on the nerve terminal that subsequently reduce ACh release.
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