Increased vulnerability of brain to estrogen withdrawal-induced mitochondrial dysfunction with aging.
In the present study, to determine whether aging could increase the vulnerability of the brain to estrogen withdrawal-induced mitochondrial dysfunction, we measured the cytochrome c oxidase (COX) activity and mitochondrial adenosine triphosphate (ATP) content in hippocampi of 2 groups of ovariectomized (OVX) Wistar rats aged 2 months (young) and 9 months (middle-aged), respectively. In addition, effects of genistein and estradiol benzoate (EB) were tested also. We observed only a transient alteration of COX activity and mitochondrial ATP content in hippocampi of young OVX rats but a prolonged lowering of COX activity and mitochondrial ATP content in hippocampi of middle-aged OVX rats. This suggested that with aging compensatory mechanisms of mitochondrial function were attenuated, thus exacerbated estrogen withdrawal-induced mitochondrial dysfunction in hippocampi. Significantly, EB/genistein treatment reversed this estrogen withdrawal-induced mitochondrial dysfunction in both young and middle-aged rats suggesting that genistein may be used as a substitute for estradiol to prevent age-related disease such as Alzheimer's disease in post-menopausal females.
Shi
Chun
C
Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
Xu
Jie
J
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D010052:Ovariectomy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D004967:Estrogens; D000255:Adenosine Triphosphate; D011451:Prostaglandin-Endoperoxide Synthases