Possible role of mitochondrial dysfunction in central neurodegeneration of ovariectomized rats.
In the present study, ovariectomized Sprague-Dawley rats were used to mimic the pathological changes of post-menopausal females with genistein and estradiol benzoate (EB) as substitutes for endogenous estradiol. Measurements of hippocampal ATP content, mitochondrial ATP content and the rate of mitochondrial ATP synthesis in the hippocampus indicated that after ovariectomy, brain energy metabolism of the rats presented a transient change in hippocampal ATP content which was significant from the 6th to the 8th day after ovariectomy. The change on the 6th day was the most noteworthy. Mitochondrial ATP content and the rate of mitochondrial ATP synthesis of the hippocampus were also lowered. However, after using EB or genistein, the three indicators returned to normal. It is suggested that mitochondrial dysfunction may play a key role in Alzheimer's disease (AD) of the post-menopausal female, and may serve as the target for endogenous estrogen and exogenous phytoestrogen. In addition, genistein, which possesses the properties of estrogen but not its side effects such as carcinogenicity, could reverse the bioenergetic defects of ovariectomized rats and perhaps be used as a substitute for estradiol to prevent or treat central neurodegeneration in post-menopausal women.
Shi
Chun
C
Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Xu
Xiao Wu
XW
Forster
E Lucy
EL
Tang
Li Feng
LF
Ge
Zhenying
Z
Yew
David T
DT
Xu
Jie
J
D000255:Adenosine Triphosphate / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D019833:Genistein / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007279:Injections, Subcutaneous; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
C074283:estradiol 3-benzoate; D004958:Estradiol; D000255:Adenosine Triphosphate; D019833:Genistein