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Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in amyotrophic lateral sclerosis model mice.

Yoo YE, Ko CP - PLoS ONE (2012)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.

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.

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DHT increases body weight and muscle strength in SOD1 mice.A: DHT-treated SOD1 mice showed heavier body weight compared with control SOD1 mice (p<0.001), although it was still lower than the weight of WT mice throughout all time points. Orchidectomized SOD1 mice demonstrated reduced body weights compared with control SOD1 mice (p = 0.045). Data are mean ± SEM. B: The grip-strength meter was used to assess the muscle strength, and the maximum tension generated by the grip of a mouse on the pull bar was recorded. SOD1 mice exhibited diminished grip-strength compared with WT mice throughout all time points examined (p<0.0001). DHT-treated SOD1 mice showed stronger grip-strengths compared with control SOD1 mice (p<0.001), and the gap between these two groups gradually increased as age advanced. Data are mean ± SEM.
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pone-0037258-g003: DHT increases body weight and muscle strength in SOD1 mice.A: DHT-treated SOD1 mice showed heavier body weight compared with control SOD1 mice (p<0.001), although it was still lower than the weight of WT mice throughout all time points. Orchidectomized SOD1 mice demonstrated reduced body weights compared with control SOD1 mice (p = 0.045). Data are mean ± SEM. B: The grip-strength meter was used to assess the muscle strength, and the maximum tension generated by the grip of a mouse on the pull bar was recorded. SOD1 mice exhibited diminished grip-strength compared with WT mice throughout all time points examined (p<0.0001). DHT-treated SOD1 mice showed stronger grip-strengths compared with control SOD1 mice (p<0.001), and the gap between these two groups gradually increased as age advanced. Data are mean ± SEM.

Mentions: To examine whether increased muscle weight and size through a DHT implant was associated with the increase in body weight, we measured the body weight of SOD1-G93A mice. As shown in Fig. 3A, DHT-treated SOD1-G93A mice demonstrated heavier body weights compared with control SOD1-G93A mice (p<0.001), although it was not able to be rescued to the level of wild-type mice. Decreased androgen concentration in SOD1-G93A mice by orchidectomy led to further reduction in body weights compared with control SOD1-G93A mice (p = 0.045, Fig. 3A).


Dihydrotestosterone ameliorates degeneration in muscle, axons and motoneurons and improves motor function in amyotrophic lateral sclerosis model mice.

Yoo YE, Ko CP - PLoS ONE (2012)

DHT increases body weight and muscle strength in SOD1 mice.A: DHT-treated SOD1 mice showed heavier body weight compared with control SOD1 mice (p<0.001), although it was still lower than the weight of WT mice throughout all time points. Orchidectomized SOD1 mice demonstrated reduced body weights compared with control SOD1 mice (p = 0.045). Data are mean ± SEM. B: The grip-strength meter was used to assess the muscle strength, and the maximum tension generated by the grip of a mouse on the pull bar was recorded. SOD1 mice exhibited diminished grip-strength compared with WT mice throughout all time points examined (p<0.0001). DHT-treated SOD1 mice showed stronger grip-strengths compared with control SOD1 mice (p<0.001), and the gap between these two groups gradually increased as age advanced. Data are mean ± SEM.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351454&req=5

pone-0037258-g003: DHT increases body weight and muscle strength in SOD1 mice.A: DHT-treated SOD1 mice showed heavier body weight compared with control SOD1 mice (p<0.001), although it was still lower than the weight of WT mice throughout all time points. Orchidectomized SOD1 mice demonstrated reduced body weights compared with control SOD1 mice (p = 0.045). Data are mean ± SEM. B: The grip-strength meter was used to assess the muscle strength, and the maximum tension generated by the grip of a mouse on the pull bar was recorded. SOD1 mice exhibited diminished grip-strength compared with WT mice throughout all time points examined (p<0.0001). DHT-treated SOD1 mice showed stronger grip-strengths compared with control SOD1 mice (p<0.001), and the gap between these two groups gradually increased as age advanced. Data are mean ± SEM.
Mentions: To examine whether increased muscle weight and size through a DHT implant was associated with the increase in body weight, we measured the body weight of SOD1-G93A mice. As shown in Fig. 3A, DHT-treated SOD1-G93A mice demonstrated heavier body weights compared with control SOD1-G93A mice (p<0.001), although it was not able to be rescued to the level of wild-type mice. Decreased androgen concentration in SOD1-G93A mice by orchidectomy led to further reduction in body weights compared with control SOD1-G93A mice (p = 0.045, Fig. 3A).

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.

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.

Show MeSH
Related in: MedlinePlus