Different impact of ALS on laminin isoforms in human extraocular muscles versus limb muscles.

Abstract

PURPOSE:

To determine the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the laminin isoform composition of the basement membranes (BMs) in EOMs and limb muscles from donors with ALS.

METHODS:

Muscle samples collected at autopsy from ALS donors and from transgenic mice overexpressing human superoxide dismutase type I mutations (D90A or G93A), and age-matched controls were analyzed with immunohistochemistry using antibodies against laminin chain (Ln)α2, Lnα4, Lnα5, Lnβ1, Lnβ2, and Lnγ1. Neuromuscular junctions (NMJs) were identified with α-bungarotoxin.

RESULTS:

Lnα2, the hallmark chain of skeletal muscle, and Lnβ2 were absent or partially absent from the BMs in a variable number of muscle fibers in most of the ALS EOMs. Three ALS donors showed dramatic decrease in the levels of these chains around their muscle fibers and NMJs. Changes in Lnα2 were not age related and were also present in EOMs of ALS mouse models. Lnα4 was preserved in the majority of NMJs in EOMs but absent in the majority of NMJs in limb muscle of ALS. The BMs around muscle fibers, NMJs, nerves, and blood vessels of the majority of EOMs of ALS donors had rather normal appearance and laminin composition, but heterogeneity was observed among EOM samples of individual ALS donors and between ALS donors.

CONCLUSIONS:

The present study showed distinct impact of ALS on EOMs compared with limb muscles. The EOMs maintained a normal laminin composition in their NMJs, which may be instrumental for the fact that they are not typically affected in ALS.

• Authors: Jing-Xia Liu, Thomas Brännström, Peter M Andersen, Fatima Pedrosa-Domellöf
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 52 Issue 7 Pg. 4842-52 (Jul 01 2011) ISSN: 1552-5783 [Electronic] United States
• PMID: 21372009 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Laminin
• Protein Isoforms
• Myosin Heavy Chains

Topics

• Aged
• Aged, 80 and over
• Amyotrophic Lateral Sclerosis (immunology, metabolism, pathology)
• Animals
• Basement Membrane (metabolism)
• Extremities
• Female
• Humans
• Immunity, Cellular
• Immunohistochemistry
• Laminin (immunology, metabolism)
• Male
• Mice
• Mice, Transgenic
• Middle Aged
• Muscle, Skeletal (metabolism, pathology)
• Myosin Heavy Chains (genetics)
• Oculomotor Muscles (metabolism, pathology)
• Protein Isoforms