Estradiol activates PI3K/Akt/GSK3 pathway under chronic neurodegenerative conditions triggered by perinatal asphyxia

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.Fil: Saraceno, Gustavo Ezequiel. Universite de Bordeaux; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Bellini, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Garcia Segura, Luis Miguel. Consejo Superior de Investigaciones Científicas; España. Instituto de Salud Carlos III; EspañaFil: Capani, Francisco. Universidad Autónoma de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin

Cortical spreading depression and mitochondrial dysfunction with aging: lessons from ethanol abuse

Chronic consumption of ethanol has a damaging effect in various organs and metabolic functions, including liver, kidney, heart, pancreas, and brain (Sun and Sun, 2001; Bezerra Rde et al., 2005). Additionally, it has been shown that both the acute and chronic ethanol intake induce alteration in voltage-gated channels causing behavioral and electrophysiological changes in the brain (Little, 1999). In the last few years, the effect of ethanol in the electrophysiological phenomenon, known as cortical spreading depression (CSD), has been widely assessed (Sonn and Mayevsky, 2001; Bezerra Rde et al., 2005; Abadie-Guedes et al., 2008) as an important model to predict the damaging effects of ethanol in both young and aged brains.Fil: Barreto, George E.. Pontificia Universidad Javeriana; ColombiaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Cabezas, Ricardo. Pontificia Universidad Javeriana; Colombi

Expression of Thioredoxin Family Proteins During Perinatal Asphyxia

Background: Alterations in the gas exchange in the placenta and fetus lungs malfunction in humans can lead to perinatal asphyxia (PA). Every organ in the body is affected by PA, yet it is particularly deleterious for the central nervous system (CNS). The reoxygenation that follows a PA event produces a great quantity of ROS, which can ultimately lead to irreversible changes in the redox balance. Thioredoxins (Trxs) are a group of proteins that are closely involved in redox regulation and have been recognized as the most important regulators of the thiol redox state. In the present study, we analyze the changes in Trxs expression and distribution in hippocampus, striatum and cerebellum caused by PA, in 30 days-old rats.Method: The model for common carotid artery ligation used in this study mimics PA in murine animals. On post-natal day seven, Sprague-Dawley rats were subjected to a ligation of the common carotid artery, followed by nitrogen exposure (HI group) or sham-operation procedures (ctrl group). Animals were euthanized, and the obtained samples were analyzed by Western blot, ELISA and immunohistochemistry.Results and conclusions: Our data showed changes in the expression of Prx2, Trx1, Trx2, Grx2, Grx5 and TrxR1. This study shows the complexity of the expression and distribution of Trxs in the different areas of the CNS and sheds light on the importance of some of the Trxs family members in PA, and thus, as possible targets for therapeutic interventions

Neuroactivesteroids as neuroprotective agents against the neurodegenerative effects induced by perinatal hypoxia-ischemia injury

Hypoxic-ischemic (HI) brain injury is one of main causes of long-term neurologic disability, morbidity and death worldwide in adults and children. This public health concern is mainly characterized by a decrease in oxygen concentration and blood flow to the tissues, which lead to cell death by energy depletion and increases free radical generation and inflammation, caused by an inefficient supply of nutrients to the brain. Hypoxic-ischemic brain injury occurs in perinatal asphyxia (PA), an obstetric complication associated with an impaired gas exchange. The incidence of PA is estimated at 1/1000 live births in developed countries. Currently, there are no effective pharmaceutical strategies to prevent the triggering of secondary injury cascades, including oxidative stress and metabolic dysfunction. Neuroactive steroids like selective estrogen receptor modulators, SERMs, exert severalneuroprotective effects. ..Fil: Toro Urrego, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Luaces, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Aguilar, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentin

Metabolic Changes Following Perinatal Asphyxia: Role of Astrocytes and Their Interaction with Neurons

Perinatal Asphyxia (PA) represents an important cause of severe neurological deficits including delayed mental and motor development, epilepsy, major cognitive deficits and blindness. The interaction between neurons, astrocytes and endothelial cells plays a central role coupling energy supply with changes in neuronal activity. Traditionally, experimental research focused on neurons, whereas astrocytes have been more related to the damage mechanisms of PA. Astrocytes carry out a number of functions that are critical to normal nervous system function, including uptake of neurotransmitters, regulation of pH and ion concentrations, and metabolic support for neurons. In this work, we aim to review metabolic neuron-astrocyte interactions with the purpose of encourage further research in this area in the context of PA, which is highly complex and its mechanisms and pathways have not been fully elucidated to this day.Fil: Logica Tornatore, Tamara Maite Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Riviere, Stephanie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Holubiec, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Castilla Lozano, Maria del Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Barreto, George E.. Pontificia Universidad Javeriana; ColombiaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Universidad Argentina "John F. Kennedy"; Argentina. Universidad Autónoma de Chile; Chil

SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. A theoretical approach of our previous experiments reporting the cytoprotective effects of the Valeriana officinalis compounds extract for PD is suggested. In addiction to considering the PD as a result of mitochondrial metabolic imbalance and oxidative stress, such as in our previous in vitro model of rotenone, in the present manuscript we added a genomic approach to evaluate the possible underlying mechanisms of the effect of the plant extract. Microarray of substantia nigra (SN) genome obtained from Allen Brain Institute was analyzed using gene set enrichment analysis to build a network of hub genes implicated in PD. Proteins transcribed from hub genes and their ligands selected by search ensemble approach algorithm were subjected to molecular docking studies, as well as 20 ns Molecular Dynamics (MD) using a Molecular Mechanic Poison/Boltzman Surface Area (MMPBSA) protocol. Our results bring a new approach to Valeriana officinalis extract, and suggest that hesperidin, and probably linarin are able to relieve effects of oxidative stress during ATP depletion due to its ability to binding SUR1. In addition, the key role of valerenic acid and apigenin is possibly related to prevent cortical hyperexcitation by inducing neuronal cells from SN to release GABA on brain stem. Thus, under hyperexcitability, oxidative stress, asphyxia and/or ATP depletion, Valeriana officinalis may trigger different mechanisms to provide neuronal cell protection.Fil: Santos, Gesivaldo. Universidade Estadual do Sudoeste da Bahia; BrasilFil: Giraldez Alvarez, Lisandro Diego. Universidade Estadual do Sudoeste da Bahia; BrasilFil: Ávila Rodriguez, Marco. Pontificia Universidad Javeriana; ColombiaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Galembeck, Eduardo. Universidade Estadual de Campinas; BrasilFil: Gôes Neto, Aristóteles. Universidade Estadual de Feira de Santana; BrasilFil: Barreto, George E.. Pontificia Universidad Javeriana; ColombiaFil: Andrade, Bruno. Universidade Estadual do Sudoeste da Bahia; Brasi

Immune System Links Psoriasis-Mediated Inflammation to Cardiovascular Diseases via Traditional and Non-Traditional Cardiovascular Risk Factors

Background. Cutaneous psoriasis and psoriatic arthritis increase the risk of cardiovascular diseases though the reasons are not clear. Here we discuss the role of the immune system in atherosclerosis and of the proinflammatory status in psoriasis and psoriatic arthritis diseases

Glial modulation by N-acylethanolamides in brain injury and neurodegeneration

Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs), naturally occurring amides, are known for their pro-homeostatic effects. An increase in NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells.Fil: Herrera, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Kolliker Frers, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Barreto, George. Pontificia Universidad Javeriana; ColombiaFil: Blanco, Eduardo. Universidad de Lleida; EspañaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Universidad Argentina "John F. Kennedy"; Argentin