期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 57, 期 15, 页码 6831-6842出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.16-20074
关键词
extraocular muscles; neuromuscular junctions; neurotrophin; amyotrophic lateral sclerosis; neurotrophic factor
资金
- Swedish Research Council [2015-02438]
- Kronprinsessan Margaretas Arbetsnamnd for Synskadade
- Swedish Medical Society
- Bjorklunds Fond
- Swedish Association for the Neurologically Disabled
- Ogonfonden
- Vinnova [2015-02438] Funding Source: Vinnova
- Swedish Research Council [2015-02438] Funding Source: Swedish Research Council
PURPOSE. To investigate the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the distribution of neurotrophic factors (NTFs) and their receptors in EOMs and limb muscles from ALS transgenic mice. METHODS. Muscle samples collected from transgenic mice overexpressing human superoxide dismutase type 1 mutations (SOD1G93A, the most widely used mouse model of ALS) at 50 and 150 days as well as age-matched controls were analyzed with immunohistochemistry using antibodies against brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4), glial cell line-derived neurotrophic factor (GDNF), and the neurotrophin receptors p75(NTR), tyrosine kinase (Trk) receptor TrkB and TrkC, and GDNF family receptor alpha-1 (GFR alpha-1). RESULTS. There was an intrinsic difference in NTF expression between EOMs and limb muscles in control mice: EOMs presented significantly lower number of neuromuscular junctions (NMJs) labeled for BDNF and NT-4 at 50 days, and for BDNF and GDNF at 150 days, compared with the control limb muscles of corresponding age. In ALS transgenic mice at 150 days, NTF expression in limb muscles was significantly changed but not in EOMs: the limb muscles presented a significant decline in the number of NMJs labeled for BDNF, NT-4, GDNF, p75(NTR), TrkB, and TrkC, which was not observed in EOMs. CONCLUSIONS. The significant differences in expression of NTFs on NMJs between EOMs and limb muscles in both control and ALS transgenic mice suggest that NTF may be involved in the pathogenesis of ALS and the resistance of EOMs to the disease.
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