Effects of estrogen on lifespan and motor functions in female hSOD1 G93A transgenic mice.
Amyotrophic lateral sclerosis (ALS) is a progressive disease which is caused by degeneration of motor neurons in the central nervous system. The incidence of ALS is higher in men than women, but the female advantage disappears with increased age. Here, we report evidence that the female advantage is due to the protective role of estrogen. In an ALS mouse model carrying the human Cu/Zn superoxide dismutase (hSOD1) G93A transgene, ovariectomy did not alter the onset age of the disease while reducing the female lifespan by 7 days and making it comparable to that of the male transgenic mice. Treatment of ovariectomized females with 17beta-estradiol (E2) did not delay the onset of disease, but prevented progression of ALS motor dysfunctions as shown by extension reflex test for a limited time window. Importantly, E2 treatment rescued the lifespans in overiectomized females. These findings will provide important new insights to interpretation of disease progression in post-menopausal female ALS patients.
Choi
Chan-Il
CI
Department of Anatomy, Ajou University, School of Medicine, Suwon, Republic of Korea.
Lee
Young-Don
YD
Gwag
Byoung Joo
BJ
Cho
Sung Ig
SI
Kim
Sung-Soo
SS
Suh-Kim
Haeyoung
H
D017668:Age of Onset; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004958:Estradiol / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy / Q000379:methods; D011336:Probability; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000235:genetics*
D004967:Estrogens; D004958:Estradiol; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase