17¦Â-Estradiol and genistein acute treatments improve some cerebral cortex homeostasis aspects deteriorated by aging in female rats

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• 作者：Javier Morá ; n ^{moranjavier.uo@uniovi.es} ; Pablo Garrido ^{garridopablo@uniovi.es} ; Ana Alonso ^{alonsoana@uniovi.es} ; Estefaní ; a Cabello ^{UO157195@uniovi.es} ; Celestino Gonzá ; lez ; ^{tinog@uniovi.es}
• 关键词：GLUT ; glucose transporter ; CO ; cytochrome c oxidase ; ER ; estrogen receptor ; CNS ; central nervous system ; SERMs ; selective estrogen receptor modulators ; YE ; young animals treated with estradiol ; AE ; aged animals treated with estradiol ; YG1 ; young animals t
• 刊名：Experimental Gerontology
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：48
• 期：4
• 页码：414-421
• 全文大小：672 K

文摘

Aging is associated with decreased insulin sensitivity and impaired cerebral glucose homeostasis. These changes increase neural sensitivity to metabolic damage contributing to cognitive decline, being the decrease in plasma estrogen following menopause one of the main factors involved in aged females. Phytoestrogens as genistein are structurally similar to 17¦Â-estradiol, bind to estrogen receptors, and can evoke both estrogenic and anti-estrogenic effects. Estrogens and phytoestrogens have neuroprotective potential, but the physiological mechanisms are not fully understood. Young and aged female Wistar rats were ovariectomized and treated acutely with 17¦Â-estradiol (1.4 ¦Ìg/kg body weight), genistein (10 or 40 mg/kg body weight), or vehicle. Cortical expression of glucose transporter-3 (GLUT-3) and -4 (GLUT-4), cytochrome c oxidase (CO), estrogen receptor-¦Á (ER¦Á) and -¦Â (ER¦Â) was measured by Western blotting. There was an age-related decline in GLUT-4, CO and ER¦Â levels. Both drugs, estradiol and genistein, were able to reverse GLUT-3 downregulation in the cortex following late ovariectomy. However, genistein was the only treatment able to restore completely GLUT-4 levels in aged rats. In contrast, estradiol was more potent than genistein at increasing CO, a marker of cerebral oxidative metabolism. As regards ER levels, estradiol increased the ER¦Á67 quantity diminished by late ovariectomy, while genistein did the same with the other ER¦Á isoform, ER¦Á46, highlighting drug-specific differences in expression changes for both isoforms. On the other hand, no treatment-related differences were found regarding ER¦Â levels. Therefore, genistein like estradiol could be suitable treatments against cortical metabolic dysfunction caused by aging. These treatments may hold promise as neuroprotective strategies against diabetes and age-related neurodegenerative diseases.