title: Analysis of neurotrophic factors in limb and extraocular muscles of mouse model of amyotrophic lateral sclerosis.
abstract: 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.
authors.affiliation: Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Vahid M
authors.initials: VM
authors.lastname: Harandi
authors.affiliation: Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lindquist
authors.affiliation: Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Shrikant Shantilal
authors.initials: SS
authors.lastname: Kolan
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brännström
authors.affiliation: Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Jing-Xia
authors.initials: JX
authors.lastname: Liu
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; C073922:neurotrophin 4