Chronic estradiol treatment improves brain homeostasis during aging in female rats.
Aging is associated with a reduction in metabolic function, insulin resistance, increased incidence of neurodegenerative diseases, and memory or cognitive dysfunction. In aging females, loss of gonadal function determines the beginning of the period of reduced metabolic function. Estrogens have neuroprotective effects, but the mechanisms by which they exert these effects remain unclear. The effects of estradiol treatment on the activation of the insulin receptor substrate (IRS)-1 signaling pathway, the interactions between estrogen receptor (ER)-alpha and IRS-1 and the p85alpha subunit of phosphatidylinositol-3 kinase, together with the possible effects of estradiol treatment on glucose transporter-3 and -4 levels, were investigated in female rats. The level of expression of each glucose transporter was greater in control and estradiol-treated groups than in the ovariectomized group. Interactions of ERalpha46-IRS-1, ERalpha46-p85alpha, and p85alpha-IRS-1, as well as IRS-1 phosphorylation, appeared to increase with estradiol treatment. The results indicate that estradiol treatment improves some aspects of neuronal homeostasis that are affected by aging; this may indicate that estradiol has neuroprotective effects in female rats. Additional animal studies are required to clarify the neuroprotective role of estradiol in relation to other important molecules involved in the IRS-1-phosphatidylinositol-3 kinase signaling pathway.
Alonso
Ana
A
Department of Functional Biology, University of Oviedo, Oviedo, Spain.
Moreno
María
M
Ordóñez
Patricia
P
Fernández
Rebeca
R
Pérez
Cristina
C
Díaz
Fernando
F
Navarro
Ana
A
Tolivia
Jorge
J
González
Celestino
C
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D055504:Insulin Receptor Substrate Proteins; D018696:Neuroprotective Agents / Q000097:blood / Q000494:pharmacology; D010052:Ovariectomy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D047628:Estrogen Receptor alpha; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D018696:Neuroprotective Agents; C495690:Slc2a3 protein, rat; C495694:Slc2a4 protein, rat; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases