Gonadectomy and dehydroepiandrosterone (DHEA) do not modulate disease progression in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis

Abstract

Epidemiological studies have shown a higher incidence of amyotrophic lateral sclerosis (ALS) in men than women. Interestingly, there are clear gender differences in disease onset and progression in rodent models of familial ALS overexpressing mutated human superoxide dismutase-1 (SOD1-G93A). In the present study we sought to determine whether the alterations of serum steroid levels by gonadectomy or chronic treatment of neuroprotective neurosteroids can modulate disease onset and progression in a rat model of ALS (SOD1-G93A transgenic rats). Presymptomatic SOD1-G93A rats were gonadectomized or treated with a neurosteroid dehydroepiandrosterone (DHEA) using silastic tubing implants. Disease onset and progression of the animals were determined by the routine analyses of locomotor testing using the Basso-Beattie-Bresnahan (BBB) score. Although sexual dimorphism was observed in intact and gonadectomized SOD1-G93A rats, there was no significant effect of gonadectomy on disease onset and progression. DHEA treatment did not alter disease progression or survival in SOD1-G93A rats. Our results indicate that gonadal steroids or neurosteroids are not one of the possible modulators for the occurrence or disease progression in a rat model of ALS. Further analysis will be necessary to understand how sexual dimorphism is involved in ALS disease progression.

Key words::

• Amyotrophic lateral sclerosis (ALS)
• SOD1-G93A rats
• sexual dimorphism
• gonadectomy
• dehydroepiandrosterone (DHEA)

Acknowledgements

This work was supported by grants from the ALS Association, NIH/NINDS (to CNS and MS), The University of Wisconsin Foundation, and the Les Turner ALS foundation. This project was also supported in part by the UW Institute for Clinical and Translational Research through an NIH Clinical and Translational Science Award, grant 1 UL1 RR025011. The DHEA analysis was performed by Dan Wittwer and supported in part by the Wisconsin National Primate Research Center, RR000167, a component of the National Institutes of Health.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.