The protective effect of growth hormone on Cu/Zn superoxide dismutase-mutant motor neurons

BMC Neuroscience

Manho Kim¹  Hyun-Jung Kim²  Jin-Young Chung³ 

[1] Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, 101 Daehakro, Chongno-ku, Seoul, 110-744, South Korea;Department of Neurology, Seoul National University Hospital, 101 Daehakro, Chongno-ku, Seoul, 110-744, South Korea;Department of Veterinary Internal Medicine and Geriatrics, Kangwon National University, Gangwondo, South Korea

关键词: Mutated SOD1;    Growth hormone (GH);    Amyotrophic lateral sclerosis (ALS);   

Others  :  1122549
DOI  :  10.1186/s12868-015-0140-z

 received in 2014-08-07, accepted in 2015-01-21,  发布年份 2015

【 摘 要 】

Background

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. The gene encoding Cu/Zn superoxide dismutase (SOD1) is responsible for 20% of familial ALS cases. Growth hormone (GH) concentrations are low in the cerebrospinal fluid of patients with ALS; however, its association with motoneuronal death is not known. We tested the neuroprotective effects of GH on human SOD-1-expressing cultured motor neurons and SOD1G93A transgenic mice.

Results

In cultured motor neurons, cytotoxicity was induced by A23187, GNSO, or homocysteine, and the effects of GH were determined by MTT, bax, PARP cleavage pattern, Hoechst nuclear staining, MAPK, and PI3K assay. In SOD-1 transgenic mice, rotarod motor performance was evaluated. Survival analysis of motoneuronal loss was done using cresyl violet, GFAP, and Bcl-2 staining. GH prevents motorneuronal death caused by GSNO and homocysteine, but not that by A23187. It activates MAPK and PI3K. GH-treated mice showed prolonged survival with improved motor performance and weight loss. GH decreased cresyl violet positive motoneuronal loss with strong Bcl-2 and less GFAP immunoreactivity.

Conclusions

Our results demonstrate that GH has a protective effect on mutant SOD-1-expressing motor neurons.

【 授权许可】

   
2015 Chung et al.; licensee BioMed Central.

【 图 表 】

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