Morphological differences between wild-type and transgenic superoxide dismutase 1 lumbar motoneurons in postnatal mice.

J Comp Neurol

UMR 6196, Centre National de la Recherche Scientifique, Laboratoire de Plasticité et Physiopathologie de la Motricité, Université de la Méditerranée, 13402 Marseille Cedex 20, France.

Published: November 2008

Quantitative analysis of the dendritic arborizations of wild-type (WT) and superoxide dismutase 1 (SOD1) postnatal mouse motoneurons was performed following intracellular staining and 3D reconstructions with Neurolucida system. The population of lumbar motoneurons was targeted in the caudal part of the L5 segment, and all labeled motoneurons were located within the same ventrolateral pool. Despite the similar size of the soma and the mean diameter of primary dendrites, the dendritic arborizations of the WT and SOD1 motoneurons showed significant differences in terms of their morphometric parameters. The metric and topological parameters of dendrites show that the total dendritic length and surface area and total number of segments, branching nodes, and tips per motoneuron were significantly higher in SOD1 motoneurons. Our main finding concerns a proliferation of dendritic branches starting at about 100 microm from the soma in the SOD1 motoneurons. However, the longest and mean dendritic paths from soma to terminations were similar, giving a comparable envelope of the dendritic fields. Indeed, the SOD1 motoneurons were larger as a result of abnormal branching. The results suggest that a defect in pruning mechanisms occurs during this developmental period. The abnormal growth of the dendritic arborizations and the reduced excitability of postnatal SOD1 motoneurons could be a neuroprotective response and would represent an early compensatory mechanism against the activity-induced toxicity.

Download full-text PDF

Source
http://dx.doi.org/10.1002/cne.21818DOI Listing

Publication Analysis

Top Keywords

sod1 motoneurons
20
dendritic arborizations
12
motoneurons
9
superoxide dismutase
8
lumbar motoneurons
8
dendritic
7
sod1
6
morphological differences
4
differences wild-type
4
wild-type transgenic
4

Similar Publications

Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disease of motor neurons, presenting with relentlessly progressive muscle atrophy and weakness. More than fifty genes carrying causative or disease-modifying variants have been identified since the 1990s, when the first ALS-associated variant in the gene SOD1 was discovered. The most commonly mutated ALS genes in the European populations include the C9orf72, SOD1, TARDBP and FUS.

View Article and Find Full Text PDF

Neurodegeneration refers to the gradual loss of neurons and extensive changes in glial cells like tau inclusions in astrocytes and oligodendrocytes, α-synuclein inclusions in oligodendrocytes and SOD1 aggregates in astrocytes along with deterioration in the motor, cognition, learning, and behavior. Common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), spinocerebellar ataxia (SCA), and supranuclear palsy. There is a lack of effective treatment for neurodegenerative diseases, and scientists are putting their efforts into developing therapies against them.

View Article and Find Full Text PDF

In amyotrophic lateral sclerosis (ALS), early mitochondrial dysfunction may contribute to progressive motor neuron loss. Remarkably, the ectopic expression of the Orthobornavirus bornaense type 1 (BoDV-1) X protein in mitochondria blocks apoptosis and protects neurons from degeneration. Therefore, this study examines the neuroprotective effects of X protein in an ALS mouse model.

View Article and Find Full Text PDF

Investigating the impact of SOD1 mutations on amyotrophic lateral sclerosis progression and potential drug repurposing through analysis.

J Biomol Struct Dyn

December 2024

Department of Medical Laboratory Technology, Faculty of Medical Applied Science, Northern Border University, Arar, Saudi Arabia.

Superoxide dismutase 1 (SOD1) is a vital enzyme responsible for attenuating oxidative stress through its ability to facilitate the dismutation of the superoxide radical into oxygen and hydrogen peroxide. The progressive loss of motor neurons characterize amyotrophic lateral sclerosis (ALS), a crippling neurodegenerative disease that is caused by mutations in the SOD1 gene. In this study, mutational analysis was performed to study the various mutations, the pathogenicity and stability ΔΔG (binding free energy) of the variant of SOD1.

View Article and Find Full Text PDF

Lipid nanoparticles and transcranial focused ultrasound enhance the delivery of SOD1 antisense oligonucleotides to the murine brain for ALS therapy.

J Control Release

December 2024

School of Chemistry and Molecular Bioscience, Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia. Electronic address:

Article Synopsis
  • ALS is a severe neurodegenerative disease characterized by the buildup of misfolded proteins in motor neurons, prompting researchers to find ways to reduce this burden for potential treatment.
  • Antisense oligonucleotides (ASOs) have been identified as a promising option to target proteins like SOD1 that cause mutations, but their delivery to the central nervous system is challenging due to the blood-brain barrier.
  • The study demonstrates that using transcranial focused ultrasound (FUS) along with calcium phosphate lipid nanoparticles significantly enhances the delivery of a SOD1 ASO into the brain of mice, leading to reduced SOD1 levels and improved motor neuron survival without damaging brain tissue.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!