Analysis of Neurotrophic Factors in Limb and Extraocular Muscles of Mouse Model of Amyotrophic Lateral Sclerosis
| Autor: | Jing-Xia Liu, Vahid M. Harandi, Thomas Brännström, Shrikant S. Kolan, Susanne Lindquist |
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| Rok vydání: | 2014 |
| Předmět: |
Nervous system
Pathology Cell- och molekylärbiologi neurotrophins Nervous System Mice Neurotrophin 3 Neurotrophic factors Medicine and Health Sciences Glial cell line-derived neurotrophic factor Amyotrophic lateral sclerosis neurotrophic factor Musculoskeletal System Motor Neurons Multidisciplinary biology Muscles Neurodegenerative Diseases medicine.anatomical_structure Neurology extraocular muscles Medicine Anatomy limb muscles Research Article Genetically modified mouse Muscle tissue medicine.medical_specialty Science Research and Analysis Methods Extraocular muscles Ocular System medicine Animals Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Animal Models of Disease Muscle Skeletal Brain-Derived Neurotrophic Factor Amyotrophic Lateral Sclerosis Biology and Life Sciences Motor neuron medicine.disease Motor System Disease Models Animal Skeletal Muscles Oculomotor Muscles Animal Studies biology.protein ALS Cell and Molecular Biology Neuroscience |
| Zdroj: | PLoS ONE, Vol 9, Iss 10, p e109833 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0109833 |
| Popis: | Amyotrophic lateral sclerosis (ALS) is currently an incurable fatal motor neuron syndrome characterized by progressive weakness, muscle wasting and death ensuing 3–5 years after diagnosis. Neurotrophic factors (NTFs) are known to be important in both nervous system development and maintenance. However, the attempt to translate the potential of NTFs into the therapeutic options remains limited despite substantial number of approaches, which have been tested clinically. Using quantitative RT-PCR (qRT-PCR) technique, the present study investigated mRNA expression of four different NTFs: brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4) and glial cell line-derived neurotrophic factor (GDNF) in limb muscles and extraocular muscles (EOMs) from SOD1G93A transgenic mice at early and terminal stages of ALS. General morphological examination revealed that muscle fibres were well preserved in both limb muscles and EOMs in early stage ALS mice. However, in terminal ALS mice, most muscle fibres were either atrophied or hypertrophied in limb muscles but unaffected in EOMs. qRT-PCR analysis showed that in early stage ALS mice, NT-4 was significantly down-regulated in limb muscles whereas NT-3 and GDNF were markedly up-regulated in EOMs. In terminal ALS mice, only GDNF was significantly up-regulated in limb muscles. We concluded that the early down-regulation of NT-4 in limb muscles is closely associated with muscle dystrophy and dysfunction at late stage, whereas the early up-regulations of GDNF and NT-3 in EOMs are closely associated with the relatively well-preserved muscle morphology at late stage. Collectively, the data suggested that comparing NTFs expression between limb muscles and EOMs from different stages of ALS animal models is a useful method in revealing the patho-physiology and progression of ALS, and eventually rescuing motor neuron in ALS patients. |
| Databáze: | OpenAIRE |
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