Estradiol Activates PI3K/Akt/GSK3 Pathway Under Chronic Neurodegenerative Conditions Triggered by Perinatal Asphyxia
| Autor: | María José Bellini, Francisco Capani, Luis M. Garcia-Segura, G. Ezequiel Saraceno |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD purl.org/becyt/ford/3.5 [https] Estrogen receptor Western blot Hippocampus Neuroprotection Neuronal survival 03 medical and health sciences 0302 clinical medicine Growth factor receptor Internal medicine medicine Pharmacology (medical) GSK3B Protein kinase B PI3K/AKT/mTOR pathway Original Research Pharmacology Signaling pathway business.industry lcsh:RM1-950 medicine.disease Otras Ciencias Médicas Perinatal asphyxia lcsh:Therapeutics. Pharmacology 030104 developmental biology Endocrinology Ciencias Médicas purl.org/becyt/ford/3 [https] Signal transduction business 030217 neurology & neurosurgery |
| Zdroj: | SEDICI (UNLP) Universidad Nacional de La Plata instacron:UNLP Frontiers in Pharmacology Frontiers in Pharmacology, Vol 9 (2018) CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2018.00335 |
| Popis: | Perinatal asphyxia (PA) remains as one of the most important causes of short-term mortality, psychiatric and neurological disorders in children, without an effective treatment. In previous studies we have observed that the expression of different neurodegenerative markers increases in CA1 hippocampal area of 4-months-old male rats born by cesarean section and exposed for 19 min to PA. We have also shown that a late treatment with 17β estradiol (daily dose of 250 μg/kg for 3 days) was able to revert the brain alterations observed in those animals. Based on these previous results, the main aim of the present study was to explore the mechanism by which the estrogenic treatment is involved in the reversion of the chronic neurodegenerative conditions induced by PA. We demonstrated that estradiol treatment of adult PA exposed animals induced an increase in estrogen receptor (ER) a and insulin-like growth factor receptor (IGF-1R) protein levels, an activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta/β-catenin signaling pathway and an increase in Bcl-2/Bax ratio in the hippocampus in comparison to PA exposed animals treated with vehicle. Taking together, our data suggest that the interaction between ERa and IGF-IR, with the subsequent downstream activation, underlies the beneficial effects of estradiol observed in late treatment of PA. Instituto de Investigaciones Bioquímicas de La Plata |
| Databáze: | OpenAIRE |
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