title: Trehalose decreases mutant SOD1 expression and alleviates motor deficiency in early but not end-stage amyotrophic lateral sclerosis in a SOD1-G93A mouse model.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder for which there is currently no effective treatment. Studies indicate that enhancing autophagy in mouse models of neurodegenerative disease can ameliorate the behavioral symptoms and pathological damage associated with the accumulation of pathological mutant proteins such as mutant superoxide dismutase (SOD1). This study investigated the effects of trehalose treatment on both early and end-stage disease in a transgenic mouse model of ALS via short-term (30 days after administration) and long-term (from 60 days after administration to death) trehalose treatment experiments. Sixty-day-old female SOD1-G93A transgenic mice were treated daily with 2% (w/v) trehalose in their drinking water for 30 days and monitored until they reached a neurological score of four, whereupon they were euthanized by cervical dislocation. Neurological, rotarod performance test and hanging wire test scores were recorded and body weight monitored. After death, the spinal cord was removed to assess the number of motor neurons and to measure the expression of mutant SOD1, LC3-II and p62. Trehalose significantly reduced the levels of mutant SOD1 and p62 and increased LC3-II in the spinal cords of 90-day-old SOD1-G93A transgenic mice. Furthermore, trehalose treatment significantly postponed disease onset, lengthened the time it took to reach a neurological score of 2 and preserved motor function; however, trehalose became less effective at delaying further disease progression as the disease progressed beyond a neurological score of 2 and it failed to extend the survival of SOD1-G93A transgenic mice. Additionally, independent of autophagy, trehalose consistently inhibited microgliosis and astrogliosis throughout the entire duration of the study. In conclusion, trehalose may be a useful add-on therapy in conjunction with other ALS treatment options to alleviate symptoms in early-stage ALS.
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China; Key Laboratory of Hebei Neurology, Shijiazhuang, China; Hebei Institute of Cardiocerebrovascular Disease, Shijiazhuang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China; Key Laboratory of Hebei Neurology, Shijiazhuang, China; Hebei Institute of Cardiocerebrovascular Disease, Shijiazhuang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China; Key Laboratory of Hebei Neurology, Shijiazhuang, China; Hebei Institute of Cardiocerebrovascular Disease, Shijiazhuang, China.
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China; Key Laboratory of Hebei Neurology, Shijiazhuang, China; Hebei Institute of Cardiocerebrovascular Disease, Shijiazhuang, China.
authors.forename: W
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China; Key Laboratory of Hebei Neurology, Shijiazhuang, China; Hebei Institute of Cardiocerebrovascular Disease, Shijiazhuang, China.
authors.forename: K
authors.initials: K
authors.lastname: Hong
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: H
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China; Key Laboratory of Hebei Neurology, Shijiazhuang, China; Hebei Institute of Cardiocerebrovascular Disease, Shijiazhuang, China. Electronic address: HBlicy5@aliyun.com.
authors.forename: C
authors.initials: C
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology*; D009460:Neurologic Examination; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D014199:Trehalose / Q000627:therapeutic use*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D014199:Trehalose; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: Glial activation; SOD1-G93A transgenic mouse; amyotrophic lateral sclerosis; autophagy; motor deficiency; trehalose