Glycine receptors (GlyRs) belong to the family of ligand-gated cys-loop receptors and effectuate fast inhibitory neurotransmission in central nervous system (CNS). They are involved in numerous physiological processes, such as movement, respiration, and processing of sensory information, as well as in regulation of neuronal excitability in different brain regions. GlyRs play important role in the maintenance of excitatory/inhibitory balance in the hippocampus and participate in the development of various brain pathologies. In the present study, we have examined a surface expression of GlyRs by pyramidal neurons and astrocytes in control and after 30 min of oxygen-glucose deprivation (OGD) in the organotypic culture of hippocampal slices. Our investigation has demonstrated a decrease in GlyR-positive staining associated with pyramidal neurons and relative stability of GlyRs expression at the surface of astrocytes 4 hs after OGD. These data indicate that GlyRs dysfunction may represent a significant additional factor leading to enhanced neuronal damage induced by OGD. Pharmacological modulation of GlyRs is a promising venue of research for the correction of negative consequences of oxygen-glucose deficiency.
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http://dx.doi.org/10.1002/cbin.11034 | DOI Listing |
Sheng Li Xue Bao
December 2024
Department of Clinical Psychology, Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250117, China.
Glycine receptors (GlyRs) belong to the ligand-gated ion channel receptor superfamily and are widely distributed throughout the central nervous system. GlyRs are essential for maintaining visual, auditory, sensory and motor functions, and abnormalities in its structure and function can lead to various neurological disorders. This review aims to provide an extensive analysis of the structure, function and regulatory mechanisms of GlyRs, and evaluate its role in various central nervous system diseases.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Medicinal Chemical Biology and Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, 300350, China.
The zinc-activated channel (ZAC) is an atypical mammalian cys-loop receptor (CLR) that is activated by zinc ions and protons, allowing cations to pass through. The molecular mechanism that ligands use to activate ZAC remains elusive. Here, we present three cryo-electron microscopy reconstructions of human ZAC (hZAC) under different conditions.
View Article and Find Full Text PDFMolecules
December 2024
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland.
The N-methyl-D-aspartate (NMDA) glutamate receptor is a major target of ethanol, and it is implicated in learning and memory formation, and other cognitive functions. Glycine acts as a co-agonist for this receptor. We examined whether Org24598, a selective inhibitor of glycine transporter1 (GlyT1), affects ethanol withdrawal-induced deficits in recognition memory (Novel Object Recognition (NOR) task) and spatial memory (Barnes Maze (BM) task) in rats, and whether the NMDA receptor glycine site participates in this phenomenon.
View Article and Find Full Text PDFNeurogenetics
January 2025
Department of Biochemistry, College of Medicine, University of Lagos, Lagos State, Nigeria.
Schizophrenia (SZ) is a complex, chronic mental disorder characterized by positive symptoms (such as delusions and hallucinations), negative symptoms (including anhedonia, alogia, avolition, and social withdrawal), and cognitive deficits (affecting attention, processing speed, verbal and visuospatial learning, problem-solving, working memory, and mental flexibility). Extensive animal and clinical studies have emphasized the NMDAR hypofunction hypothesis of SZ. Glycine plays a crucial role as an agonist of NMDAR, enhancing the receptor's affinity for glutamate and supporting normal synaptic function and plasticity, that is, signal transmission between neurons.
View Article and Find Full Text PDFInt J Neuropsychopharmacol
December 2024
Neurocrine Biosciences, Inc., San Diego, CA, United States.
Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been proposed to underlie the pathophysiology of schizophrenia, suggesting that promoting NMDAR activity may alleviate the negative or cognitive symptoms associated with schizophrenia. To circumvent excitotoxicity that may accompany direct agonism of the glutamate binding site on the NMDAR, therapeutic trials have focused on targeting the glycine binding site on the NMDAR. Direct administration of either glycine or D-serine, both of which are endogenous coagonists at the NMDAR glycine site, has yielded mixed outcomes across an array of clinical trials investigating different doses or patient populations.
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