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Nociception in the Glycine Receptor Deficient Mutant Mouse Spastic

Groemer, Teja Wolfgang; Triller, Antoine; Zeilhofer, Hanns Ulrich; Becker, Kristina; Eulenburg, Volker; Becker, Cord Michael (2022). Nociception in the Glycine Receptor Deficient Mutant Mouse Spastic. Frontiers in Molecular Neuroscience, 15:832490.

Abstract

Glycine receptors (GlyRs) are the primary mediators of fast inhibitory transmission in the mammalian spinal cord, where they modulate sensory and motor signaling. Mutations in GlyR genes as well as some other genes underlie the hereditary disorder hyperekplexia, characterized by episodic muscle stiffness and exaggerated startle responses. Here, we have investigated pain-related behavior and GlyR expression in the spinal cord of the GlyR deficient mutant mouse spastic (spa). In spastic mice, the GlyR number is reduced due to a β subunit gene (Glrb) mutation resulting in aberrant splicing of GlyRβ transcripts. Via direct physical interaction with the GlyR anchoring protein gephyrin, this subunit is crucially involved in the postsynaptic clustering of heteromeric GlyRs. We show that the mutation differentially affects aspects of the pain-related behavior of homozygous Glrbspa/Glrbspa mice. While response latencies to noxious heat were unchanged, chemically induced pain-related behavior revealed a reduction of the licking time and an increase in flinching in spastic homozygotes during both phases of the formalin test. Mechanically induced nocifensive behavior was reduced in spastic mice, although hind paw inflammation (by zymosan) resulted in allodynia comparable to wild-type mice. Immunohistochemical staining of the spinal cord revealed a massive reduction of dotted GlyRα subunit immunoreactivity in both ventral and dorsal horns, suggesting a reduction of clustered receptors at synaptic sites. Transcripts for all GlyRα subunit variants, however, were not reduced throughout the dorsal horn of spastic mice. These findings suggest that the loss of functional GlyRβ subunits and hence synaptically localized GlyRs compromises sensory processing differentially, depending on stimulus modality.

Keywords: glycine receptor; glycinergic inhibition; nociception; pain; spastic; synaptic clustering.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Molecular Biology
Life Sciences > Cellular and Molecular Neuroscience
Language:English
Date:25 April 2022
Deposited On:31 May 2022 13:39
Last Modified:27 Jan 2025 02:38
Publisher:Frontiers Research Foundation
ISSN:1662-5099
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fnmol.2022.832490
PubMed ID:35548669
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