17β-Estradiol and genistein acute treatments improve some cerebral cortex homeostasis aspects deteriorated by aging in female rats
| Autor: | Javier Morán, Celestino González, Ana Alonso, Estefanía Cabello, Pablo Garrido |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Aging
medicine.medical_specialty medicine.drug_class Ovariectomy Estrogen receptor Genistein Phytoestrogens Biology Biochemistry Neuroprotection chemistry.chemical_compound Cognition Endocrinology Internal medicine Genetics medicine Animals Humans Glucose homeostasis Rats Wistar Cognitive decline Molecular Biology Cerebral Cortex Estradiol Brain Diseases Metabolic Estrogens Cell Biology Rats Glucose Neuroprotective Agents Treatment Outcome Receptors Estrogen chemistry Estrogen Models Animal Ovariectomized rat Female Menopause Oxidation-Reduction Metabolic Networks and Pathways hormones hormone substitutes and hormone antagonists |
| Zdroj: | Experimental Gerontology. 48:414-421 |
| ISSN: | 0531-5565 |
| DOI: | 10.1016/j.exger.2013.02.010 |
| Popis: | 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 17β-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 17β-estradiol (1.4 μg/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-α (ERα) and -β (ERβ) was measured by Western blotting. There was an age-related decline in GLUT-4, CO and ERβ 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 ERα67 quantity diminished by late ovariectomy, while genistein did the same with the other ERα isoform, ERα46, highlighting drug-specific differences in expression changes for both isoforms. On the other hand, no treatment-related differences were found regarding ERβ 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. |
| Databáze: | OpenAIRE |
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