Dihydrotestosterone Ameliorates Degeneration in Muscle, Axons and Motoneurons and Improves Motor Function in Amyotrophic Lateral Sclerosis Model Mice

Hdl Handle:
http://hdl.handle.net/10675.2/710
Title:
Dihydrotestosterone Ameliorates Degeneration in Muscle, Axons and Motoneurons and Improves Motor Function in Amyotrophic Lateral Sclerosis Model Mice
Authors:
Yoo, Young-Eun; Ko, Chien-Ping
Abstract:
Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by a progressive loss of motoneurons. The clinical symptoms include skeletal muscle weakness and atrophy, which impairs motor performance and eventually leads to respiratory failure. We tested whether dihydrotestosterone (DHT), which has both anabolic effects on muscle and neuroprotective effects on axons and motoneurons, can ameliorate clinical symptoms in ALS. A silastic tube containing DHT crystals was implanted subcutaneously in SOD1-G93A mice at early symptomatic age when decreases in body weight and grip-strength were observed as compared to wild-type mice. DHT-treated SOD1-G93A mice demonstrated ameliorated muscle atrophy and increased body weight, which was associated with stronger grip-strength. DHT treatment increased the expression of insulin-like growth factor-1 in muscle, which can exert myotrophic as well as neurotrophic effects through retrograde transport. DHT treatment attenuated neuromuscular junction denervation, and axonal and motoneuron loss. DHT-treated SOD1-G93A mice demonstrated improvement in motor behavior as assessed by rota-rod and gait analyses, and an increased lifespan. Application of DHT is a relatively simple and non-invasive procedure, which may be translated into therapy to improve the quality of life for ALS patients.
Editors:
Mei, Lin
Citation:
PLoS One. 2012 May 14; 7(5):e37258
Issue Date:
14-May-2012
URI:
http://hdl.handle.net/10675.2/710
DOI:
10.1371/journal.pone.0037258
PubMed ID:
22606355
PubMed Central ID:
PMC3351454
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorYoo, Young-Eunen_US
dc.contributor.authorKo, Chien-Pingen_US
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:40:50Z-
dc.date.available2012-10-26T16:40:50Z-
dc.date.issued2012-05-14en_US
dc.identifier.citationPLoS One. 2012 May 14; 7(5):e37258en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22606355en_US
dc.identifier.doi10.1371/journal.pone.0037258en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/710-
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a lethal disease characterized by a progressive loss of motoneurons. The clinical symptoms include skeletal muscle weakness and atrophy, which impairs motor performance and eventually leads to respiratory failure. We tested whether dihydrotestosterone (DHT), which has both anabolic effects on muscle and neuroprotective effects on axons and motoneurons, can ameliorate clinical symptoms in ALS. A silastic tube containing DHT crystals was implanted subcutaneously in SOD1-G93A mice at early symptomatic age when decreases in body weight and grip-strength were observed as compared to wild-type mice. DHT-treated SOD1-G93A mice demonstrated ameliorated muscle atrophy and increased body weight, which was associated with stronger grip-strength. DHT treatment increased the expression of insulin-like growth factor-1 in muscle, which can exert myotrophic as well as neurotrophic effects through retrograde transport. DHT treatment attenuated neuromuscular junction denervation, and axonal and motoneuron loss. DHT-treated SOD1-G93A mice demonstrated improvement in motor behavior as assessed by rota-rod and gait analyses, and an increased lifespan. Application of DHT is a relatively simple and non-invasive procedure, which may be translated into therapy to improve the quality of life for ALS patients.en_US
dc.rightsYoo, Ko. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectEndocrine Systemen_US
dc.subjectEndocrine Physiologyen_US
dc.subjectHormonesen_US
dc.subjectMusculoskeletal Systemen_US
dc.subjectMuscleen_US
dc.subjectBiochemistryen_US
dc.subjectHormonesen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectNeuroscienceen_US
dc.subjectCellular Neuroscienceen_US
dc.subjectMolecular Neuroscienceen_US
dc.subjectNeurobiology of Disease and Regenerationen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectEndocrine Systemen_US
dc.subjectEndocrine Physiologyen_US
dc.subjectHormonesen_US
dc.subjectMusculoskeletal Systemen_US
dc.subjectMuscleen_US
dc.subjectDrugs and Devicesen_US
dc.subjectEndocrinologyen_US
dc.subjectEndocrine Physiologyen_US
dc.subjectHormonesen_US
dc.subjectNeurologyen_US
dc.subjectMotor Neuron Diseasesen_US
dc.subjectAmyotrophic Lateral Sclerosisen_US
dc.subjectNon-Clinical Medicineen_US
dc.titleDihydrotestosterone Ameliorates Degeneration in Muscle, Axons and Motoneurons and Improves Motor Function in Amyotrophic Lateral Sclerosis Model Miceen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3351454en_US
dc.contributor.corporatenameDepartment of Neurology-

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