Unchanged Neurotrophic Factors and Their Receptors with Sparing in Extraocular Muscles in Amyotrophic Lateral Sclerosis
(English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783Article, review/survey (Other academic) Submitted
PURPOSE. In a recent study on an amyotrophic lateral sclerosis (ALS) mouse model, we reported significant differences in mRNA levels of several neurotrophic factors (NTFs) between extraocular muscles (EOMs) and limb muscles. In order to further evaluate the possible role of NTF in the pathogenesis of ALS, we examined the distribution of the NTFs and their receptors in EOMs and limb muscles of early and late stages of SOD1G93A ALS mice.
METHODS. EOMs and limb muscles from control and ALS transgenic mice (SOD1G93A ) at early and late stages were analysed for the distribution of four different NTFs (BDNF, GDNF, NT-3, and NT-4) and their receptors (TrkB, TrkC, p75NTR, and GFR-α1) using immunohistochemistry. Labelling with NTFs at NMJs was quantified and compared between EOMs and limb muscles, and between control and SOD1G93A ALS mice.
RESULTS. NTFs and their receptors were detected in several structures in both muscle groups, including neuromuscular junctions (NMJs), intramuscular nerve axons and muscle fibres of both control and SOD1G93A ALS mice. In control mice, EOMs had lower percentage of NMJs labelled for BDNF and NT-4 at 50 days, and for BDNF, GDNF and NT-3 at 150 days, in comparison to limb muscles. In ALS mice, the percentage of NMJs labelled for BDNF, GDNF and NT-4, as well as for the receptors TrkB, TrkC, p75NTR and GFR-α1was significantly downregulated in limb muscles, but not in EOMs from early or late stage. In limb muscles from late ALS mice, the four NTFs showed no changes in intramuscular nerve axons whereas BDNF and NT-4 were increased in a number of small sized muscle fibres.
CONCLUSIONS. The significant difference in NTFs between EOMs and limb muscles in both control and ALS transgenic ALS mice, suggests that NTF are closely associated with the pathogenesis of ALS and the resistance of EOMs to the disease.
Place, publisher, year, edition, pages
neurotrophins, neurotrophic factor, extraocular muscles, ALS, nerve axons, neuromuscular junctions, SOD1G93A mice
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject Molecular Biology
IdentifiersURN: urn:nbn:se:umu:diva-120218OAI: oai:DiVA.org:umu-120218DiVA: diva2:927245