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Analysis of Neurotr...
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Vahid, Harandi M.Umeå universitet,Anatomi
(författare)
Analysis of Neurotrophic Factors in Limb and Extraocular Muscles of Mouse Model of Amyotrophic Lateral Sclerosis
- Artikel/kapitelEngelska2014
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2014-10-15
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Public Library of Science (PLoS),2014
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LIBRIS-ID:oai:DiVA.org:umu-96545
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-96545URI
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https://doi.org/10.1371/journal.pone.0109833DOI
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Språk:engelska
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Sammanfattning på:engelska
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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.
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Susanne, LindquistUmeå universitet,Pediatrik(Swepub:umu)suli0001
(författare)
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Shrikant, Shantilal KolanUmeå universitet,Anatomi(Swepub:umu)shko0002
(författare)
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Thomas, BrännströmUmeå universitet,Patologi(Swepub:umu)thbr0001
(författare)
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Jing-Xia, LiuUmeå universitet,Anatomi(Swepub:umu)liji0001
(författare)
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Umeå universitetAnatomi
(creator_code:org_t)
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Ingår i:PLOS ONE: Public Library of Science (PLoS)9:101932-6203
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