title: Effects of phytoestrogen on mitochondrial structure and function of hippocampal CA1 region of ovariectomized rats.
abstract: The present study was undertaken to evaluate whether estrogen deprivation might lead to mitochondrial alteration of hippocampal neurons of ovariectomized (OVX) rats, and to evaluate the protective effect of estrogen and phytoestrogen on the mitochondrial alteration. First, OVX rats were used to mimic the pathologic changes of neurodegeneration of postmenopausal female, and we looked into the alteration of the mitochondrial ultrastructure and ATP content of hippocampal CA1 region after ovariectomy on different phase by transmission electron microscope (TEM) and reversed-phase high-performance liquid chromatography (HPLC), and found the best phase points of the alteration of the mitochondrial ultrastructure and ATP content. Next, estrogen and phytoestrogen were administered to the OVX rats for the protective effects on the mitochondrial ultrastructure and ATP content. Meanwhile, the density, size, shape, and distribution parameters of mitochondrial ultrastructure were analyzed according to the morphometry principle. The experimental results presented that (1) The alteration of mitochondrial ultrastructure elicited by ovariectomy worsened with the days going on, and the changes were the most noteworthy in volume density (Vv), average surface area (S), specific surface area (delta), and particle dispersity (Clambdaz) on 12th day (P < 0.05 or P < 0.01). Moreover, there was no statistical significance of the numerical density (Nv) among the five groups in the first step experiment. (2) The treatment with estrogen, genistein (Gs), and ipriflavone (Ip) significantly reversed the effect elicited by ovariectomy on Vv, S, delta, Clambdaz, Nv, and particle average diameter (D) of mitochondria of hippocampal CA1 region (P < 0.05). (3) Furthermore, ATP content of hippocampal CA1 region after ovariectomy declined significantly on 7th day (P < 0.05), and estrogen and phytoestrogen could reverse the alteration (P < 0.05). Taken together, these results revealed that phytoestrogen may have a protective role against the neurodegeneration after menopause via protecting mitochondrial structure and functions. Phytoestrogen may be a good alternative as a novel therapeutic strategy for menopausal syndrome.
authors.affiliation: Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, NO.74, ZhongShan 2 Road, Guangzhou, 510080, China.
authors.forename: Xiao-Wu
authors.initials: XW
authors.lastname: Xu
authors.forename: Chun
authors.initials: C
authors.lastname: Shi
authors.forename: Zhen-Quan
authors.initials: ZQ
authors.lastname: He
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Ma
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Shen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.forename: Chuan-Jun
authors.initials: CJ
authors.lastname: Shen
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D007529:Isoflavones / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology*; D051381:Rats
chemical_list: D004967:Estrogens; D007529:Isoflavones; D018696:Neuroprotective Agents; D048789:Phytoestrogens; D004958:Estradiol; C018986:ipriflavone; D000255:Adenosine Triphosphate; D019833:Genistein