Ovariectomy and 17beta-estradiol modulate disease progression of a mouse model of ALS.
The incidence of amyotrophic lateral sclerosis (ALS) is higher among men than women but rises in women after the menopause. Estrogens may play a protective role. Treatment with estrogens has been shown to be neuroprotective in models of several neurodegenerative diseases. We therefore determined the effect of ovariectomy on female G93A mSOD1 transgenic mice, and the effect of subsequent treatment with 17beta-estradiol (E2). Ovariectomy led to a significant acceleration of disease progression of the mice, and high-dose E2 treatment significantly delayed disease progression of ovariectomized G93A mSOD1 transgenic mice. We conclude that treatment with E2 may also delay disease progression of post-menopausal women with ALS.
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, G.03.228, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
G J
GJ
Groeneveld
F L
FL
Van Muiswinkel
J M
JM
Sturkenboom
J H J
JH
Wokke
P R
PR
Bär
L H
LH
Van den Berg
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010052:Ovariectomy; D010641:Phenotype; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
D018696:Neuroprotective Agents; C000606290:SOD1 protein, human; D004958:Estradiol; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1