title: 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.
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Hayes-Punzo
authors.forename: Patrick
authors.initials: P
authors.lastname: Mulcrone
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer
authors.forename: Jacalyn
authors.initials: J
authors.lastname: McHugh
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D000818:Animals; D030801:Animals, Genetically Modified; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D003687:Dehydroepiandrosterone; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase