Early abnormalities in transgenic mouse models of amyotrophic lateral sclerosis.
type: Dataset
description: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative and fatal human disorder characterized by progressive loss of motor neurons. Transgenic mouse models of ALS are very useful to study the initial mechanisms underlying this neurodegenerative disease. We will focus here on the earlier abnormalities observed in superoxide dismutase 1 (SOD1) mutant mice. Several hypotheses have been advanced to explain the selective loss of motor neurons such as apoptosis, neurofilament disorganisation, oxidative stress, mitochondrial dysfunction, astrogliosis and excitotoxicity. Although disease onset appears at adulthood, recent studies have detected abnormalities during embryonic and postnatal maturation in animal models of ALS. We reported that SOD1(G85R) mutant mice exhibit specific delays in acquiring sensory-motor skills during the first week after birth. In addition, physiological measurements on in vitro spinal cord preparations reveal defects in evoking rhythmic activity with N-methyl-DL-aspartate and serotonin at lumbar, but not sacral roots. This is potentially significant, as functions involving sacral roots are spared at late stages of the disease. Moreover, electrical properties of SOD1 lumbar motoneurons are altered as early as the second postnatal week when mice begin to walk. Alterations concern the input resistance and the gain of SOD1 motoneurons which are lower than in control motoneurons. Whether or not the early changes in discharge firing are responsible for the uncoupling between motor axon terminals and muscles is still an open question. A link between these early electrical abnormalities and the late degeneration of motoneurons is proposed in this short review. Our data suggest that ALS, as other neurodegenerative diseases, could be a consequence of an abnormal development of neurons and network properties. We hypothesize that the SOD1 mutation could induce early changes during the period of maturation of motor systems and that compensatory mechanisms-…
landing page: 0928-4257
keyword: development
keyword: electrical-properties
keyword: infoeu-reposemanticsarticle
keyword: journal-articles
keyword: sdvneulife-sciences-q-bioneurons-and-cognition-q-bionc
keyword: sod1g85r
keyword: spinal-network
issued: 2026-05-07T04:42:12.262689
modified: 2026-05-07T04:42:12.262694
language: en
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Early abnormalities in transgenic mouse models of amyotrophic lateral sclerosis.
type: Distribution
format: HTML
access URL: https://hal.science/hal-00093914
issued: 2026-05-07T04:42:12.267090
modified: 2026-05-07T04:42:12.255323