Motoneuron subtypes show specificity in glycine receptor channel abnormalities in a transgenic mouse model of amyotrophic lateral sclerosis

Qing Chang, Lee J Martin

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective loss of motoneurons. Recently we studied glycine receptors (GlyRs) in motoneurons in an ALS mouse model expressing a mutant form of human superoxide dismutase-1 with a Gly93→Ala substitution (G93A-SOD1). Living motoneurons in dissociated spinal cord cultures were identified by using transgenic mice expressing eGFP driven by the Hb9 promoter. We showed that GlyR-mediated currents were reduced in large-sized (diameter >28 μm) Hb9-eGFP + motoneurons from G93A-SOD1 embryonic mice. Here we analyze GlyR currents in a morphologically distinct subgroup of medium-sized (diameter 10-28 μm) Hb9-eGFP + motoneurons, presumably gamma or slow-type alpha motoneurons. We find that glycine-induced current densities were not altered in medium-sized G93A-SOD1 motoneurons. No significant differences in glycinergic mIPSCs were observed between G93A-SOD1 and control medium-sized motoneurons. These results indicate that GlyR deficiency early in the disease process of ALS is specific for large alpha motoneurons.

Original languageEnglish (US)
JournalChannels
Volume5
Issue number4
StatePublished - Jul 2011

Fingerprint

Neurodegenerative diseases
Glycine Receptors
Induced currents
Amyotrophic Lateral Sclerosis
Motor Neurons
Glycine
Transgenic Mice
Superoxide Dismutase
Substitution reactions
Current density
Neurodegenerative Diseases
Spinal Cord

Keywords

  • Alpha motoneuron
  • Gamma motoneuron
  • Hb9-eGFP
  • mIPSC
  • Motoneuron culture
  • Mutant SOD1
  • Patch clamp

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

@article{8a6835436f144a1fabe22ff6d0e93dfd,
title = "Motoneuron subtypes show specificity in glycine receptor channel abnormalities in a transgenic mouse model of amyotrophic lateral sclerosis",
abstract = "Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective loss of motoneurons. Recently we studied glycine receptors (GlyRs) in motoneurons in an ALS mouse model expressing a mutant form of human superoxide dismutase-1 with a Gly93→Ala substitution (G93A-SOD1). Living motoneurons in dissociated spinal cord cultures were identified by using transgenic mice expressing eGFP driven by the Hb9 promoter. We showed that GlyR-mediated currents were reduced in large-sized (diameter >28 μm) Hb9-eGFP + motoneurons from G93A-SOD1 embryonic mice. Here we analyze GlyR currents in a morphologically distinct subgroup of medium-sized (diameter 10-28 μm) Hb9-eGFP + motoneurons, presumably gamma or slow-type alpha motoneurons. We find that glycine-induced current densities were not altered in medium-sized G93A-SOD1 motoneurons. No significant differences in glycinergic mIPSCs were observed between G93A-SOD1 and control medium-sized motoneurons. These results indicate that GlyR deficiency early in the disease process of ALS is specific for large alpha motoneurons.",
keywords = "Alpha motoneuron, Gamma motoneuron, Hb9-eGFP, mIPSC, Motoneuron culture, Mutant SOD1, Patch clamp",
author = "Qing Chang and Martin, {Lee J}",
year = "2011",
month = "7",
language = "English (US)",
volume = "5",
journal = "Channels",
issn = "1933-6950",
publisher = "Landes Bioscience",
number = "4",

}

TY - JOUR

T1 - Motoneuron subtypes show specificity in glycine receptor channel abnormalities in a transgenic mouse model of amyotrophic lateral sclerosis

AU - Chang, Qing

AU - Martin, Lee J

PY - 2011/7

Y1 - 2011/7

N2 - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective loss of motoneurons. Recently we studied glycine receptors (GlyRs) in motoneurons in an ALS mouse model expressing a mutant form of human superoxide dismutase-1 with a Gly93→Ala substitution (G93A-SOD1). Living motoneurons in dissociated spinal cord cultures were identified by using transgenic mice expressing eGFP driven by the Hb9 promoter. We showed that GlyR-mediated currents were reduced in large-sized (diameter >28 μm) Hb9-eGFP + motoneurons from G93A-SOD1 embryonic mice. Here we analyze GlyR currents in a morphologically distinct subgroup of medium-sized (diameter 10-28 μm) Hb9-eGFP + motoneurons, presumably gamma or slow-type alpha motoneurons. We find that glycine-induced current densities were not altered in medium-sized G93A-SOD1 motoneurons. No significant differences in glycinergic mIPSCs were observed between G93A-SOD1 and control medium-sized motoneurons. These results indicate that GlyR deficiency early in the disease process of ALS is specific for large alpha motoneurons.

AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective loss of motoneurons. Recently we studied glycine receptors (GlyRs) in motoneurons in an ALS mouse model expressing a mutant form of human superoxide dismutase-1 with a Gly93→Ala substitution (G93A-SOD1). Living motoneurons in dissociated spinal cord cultures were identified by using transgenic mice expressing eGFP driven by the Hb9 promoter. We showed that GlyR-mediated currents were reduced in large-sized (diameter >28 μm) Hb9-eGFP + motoneurons from G93A-SOD1 embryonic mice. Here we analyze GlyR currents in a morphologically distinct subgroup of medium-sized (diameter 10-28 μm) Hb9-eGFP + motoneurons, presumably gamma or slow-type alpha motoneurons. We find that glycine-induced current densities were not altered in medium-sized G93A-SOD1 motoneurons. No significant differences in glycinergic mIPSCs were observed between G93A-SOD1 and control medium-sized motoneurons. These results indicate that GlyR deficiency early in the disease process of ALS is specific for large alpha motoneurons.

KW - Alpha motoneuron

KW - Gamma motoneuron

KW - Hb9-eGFP

KW - mIPSC

KW - Motoneuron culture

KW - Mutant SOD1

KW - Patch clamp

UR - http://www.scopus.com/inward/record.url?scp=79960831560&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960831560&partnerID=8YFLogxK

M3 - Article

C2 - 21558795

AN - SCOPUS:79960831560

VL - 5

JO - Channels

JF - Channels

SN - 1933-6950

IS - 4

ER -