Examinando por Autor "Barreto, G.E."
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Ítem Acceso Abierto Ischemic stroke and six genetic variants in CRP, EPHX2, FGA, and NOTCH3 genes: a meta-analysis(W.B. Saunders, 2016) González-Giraldo Y.; Barreto, G.E.; Fava, C.; Forero, D.A.Background: Ischemic stroke (IS) is a leading cause of death and disability worldwide. As genetic heritability for IS is estimated at about 35%-40%, the identification of genetic variants associated with IS risk is of great importance. The main objective of this study was to carry out a meta-analysis for polymorphisms in CRP, EPHX2, FGA, and NOTCH3 genes and the risk for IS. Methods: Literature search for 6 candidate polymorphisms and IS was conducted using HuGE Navigator, PubMed, and Google Scholar databases. Meta-Analyst program was used to calculate pooled odds ratios (ORs) with a random effects model. Results: Twenty-five published studies for 6 candidate polymorphisms were included: CRP-rs1800947 (5 studies), CRP-rs1205 (3 studies), EPHX2-rs751141 (5 studies), FGA-rs6050 (6 studies), NOTCH3-rs3815188 (3 studies), and NOTCH3-rs1043994 (3 studies), for a total number of 7,825 IS cases and 56,532 control subjects. We did not find significant pooled ORs (P values > .05) for any of the genetic variants evaluated in this work. Conclusions: Our meta-analysis results did not show significant associations between these 6 polymorphisms in 4 candidate genes and IS, despite the functional role of some of these single nucleotide polymorphisms (e.g., rs6050 in FGA gene). Future studies are needed to identify additional main genetic risk factors for IS in different populations. © 2016 National Stroke Association.Ítem Acceso Abierto Metabolic and inflammatory adaptation of reactive astrocytes: role of PPARs(Humana Press Inc., 2016) Iglesias, J.; Morales, L.; Barreto, G.E.Astrocyte-mediated inflammation is associated with degenerative pathologies such as Alzheimer’s and Parkinson’s diseases and multiple sclerosis. The acute inflammation and morphological and metabolic changes that astrocytes develop after the insult are known as reactive astroglia or astrogliosis that is an important response to protect and repair the lesion. Astrocytes optimize their metabolism to produce lactate, glutamate, and ketone bodies in order to provide energy to the neurons that are deprived of nutrients upon insult. Firstly, we review the basis of inflammation and morphological changes of the different cell population implicated in reactive gliosis. Next, we discuss the more active metabolic pathways in healthy astrocytes and explain the metabolic response of astrocytes to the insult in different pathologies and which metabolic alterations generate complications in these diseases. We emphasize the role of peroxisome proliferator-activated receptors isotypes in the inflammatory and metabolic adaptation of astrogliosis developed in ischemia or neurodegenerative diseases. Based on results reported in astrocytes and other cells, we resume and hypothesize the effect of peroxisome proliferator-activated receptor (PPAR) activation with ligands on different metabolic pathways in order to supply energy to the neurons. The activation of selective PPAR isotype activity may serve as an input to better understand the role played by these receptors on the metabolic and inflammatory compensation of astrogliosis and might represent an opportunity to develop new therapeutic strategies against traumatic brain injuries and neurodegenerative diseases. © 2016 Springer Science+Business Media New YorkÍtem Acceso Abierto Neuroprotective effects of the catalytic subunit of telomerase: a potential therapeutic target in the central nervous system(Elsevier Ireland Ltd, 2016) González-Giraldo, Y.; Forero, D.A.; Echeverria, V.; Gonzalez, J.; Ávila-Rodriguez, M.; Garcia-Segura, L.M.; Barreto, G.E.Senescence plays an important role in neurodegenerative diseases and involves key molecular changes induced by several mechanisms such as oxidative stress, telomere shortening and DNA damage. Potential therapeutic strategies directed to counteract these molecular changes are of great interest for the prevention of the neurodegenerative process. Telomerase is a ribonucleoprotein composed of a catalytic subunit (TERT) and a RNA subunit (TERC). It is known that the telomerase is involved in the maintenance of telomere length and is a highly expressed protein in embryonic stages and decreases in adult cells. In the last decade, a growing number of studies have shown that TERT has neuroprotective effects in cellular and animal models after a brain injury. Significantly, differences in TERT expression between controls and patients with major depressive disorder have been observed. More recently, TERT has been associated with the decrease in reactive oxygen species and DNA protection in mitochondria of neurons. In this review, we highlight the role of TERT in some neurodegenerative disorders and discuss some studies focusing on this protein as a potential target for neuroprotective therapies. © 2016 Elsevier B.V.Ítem Acceso Abierto Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions(2016) Acaz-Fonseca E.; Avila-Rodriguez, M.; Garcia-Segura, L.M.; Barreto, G.E.In the last years there has been a considerable advance in the knowledge on the regulation of astrocytes by sex steroids under physiological and pathological conditions. By the activation of a variety of nuclear and membrane receptors, sex steroid hormones regulate the functions of astrocytes and their communication with other cell types in the central nervous system. Under physiological conditions astrocytes participate in the neuroendocrine and behavioral actions of gonadal steroids, as well as in the hormonal control of brain tissue homeostasis. Under pathological conditions astrocytes mediate, at least partially, the neuroprotective effects of gonadal steroid hormones; given that sex steroids modulate reactive astrogliosis and reduce the release of pro-inflammatory molecules by these cells. Given the side effects that sex steroids may have when administered systemically, a number of synthetic agonists of the receptors for gonadal steroid hormones in the nervous system have been developed, and may be considered for clinical use after brain injury as potential enhancers of the neuroprotective astrocytic functions. © 2016 Elsevier LtdÍtem Acceso Abierto SUR1 receptor interaction with hesperidin and linarin predicts possible mechanisms of action of Valeriana officinalis in Parkinson(Frontiers Research Foundation, 2016) Santos, G.; Giraldez-Alvarez, L.D.; Ávila-Rodriguez, M.; Capani, F.; Galembeck, E.; Neto, A.G.; Barreto, G.E.; Andrade, B.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. © 2016 Santos, Giraldez-Alvarez, ávila-Rodriguez, Capani, Galembeck, Neto, Barreto and Andrade.Ítem Acceso Abierto Testosterone protects mitochondrial function and regulates neuroglobin expression in astrocytic cells exposed to glucose deprivation(Frontiers Research Foundation, 2016) Toro-Urrego, N.; Garcia-Segura, L.M.; Echeverria, V.; Barreto, G.E.Testosterone is a hormone that has been shown to confer neuroprotection from different insults affecting the central nervous system (CNS). Testosterone induces this protection by different mechanisms that include the activation of anti-apoptotic pathways that are directly implicated in neuronal survival. However, little attention has been devoted to its actions on glial cells. In the present study, we have assessed whether testosterone exerts protection in a human astrocyte cell model, the T98G cells. Our results indicate that testosterone improves cell survival and mitochondrial membrane potential and reduces nuclear fragmentation and reactive oxygen species (ROS) generation. These effects were accompanied by a positive regulation of neuroglobin, an oxygen-binding and sensor protein, which may serve as a regulator of ROS and nitrogen reactive species (NOS), and these protective effects of testosterone may be at least in part mediated by estradiol and DHT. In conclusion, these findings suggest that astroglia may mediate some of the protective actions of testosterone in the brain upon pathological conditions. © 2016 Toro-Urrego, Garcia-Segura, Echeverria and Barreto.Ítem Acceso Abierto Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression(Elsevier Ireland Ltd, 2016) Avila-Rodriguez, M.; Garcia-Segura, L.M.; Hidalgo-lanussa, O.; Baez, E.; Gonzalez, J.; Barreto, G.E.Tibolone, a synthetic steroid used for the prevention of osteoporosis and the treatment of climacteric symptoms in post-menopausal women, may exert tissue selective estrogenic actions acting on estrogen receptors (ERs). We previously showed that tibolone protects human T98G astroglial cells against glucose deprivation (GD). In this study we have explored whether the protective effect of tibolone on these cells is mediated by ERs. Experimental studies showed that both ERα and ERβ were involved in the protection by tibolone on GD cells, being ERβ preferentially involved on these actions over ERα. Tibolone increased viability of GD cells by a mechanism fully blocked by an ERβ antagonist and partially blocked by an ERα antagonist. Furthermore, ERβ inhibition prevented the effect of tibolone on nuclear fragmentation, ROS and mitochondrial membrane potential in GD cells. The protective effect of tibolone was mediated by neuroglobin. Tibolone upregulated neuroglobin in T98G cells and primary mouse astrocytes by a mechanism involving ERβ and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ERβ and the upregulation of neuroglobin. © 2016 Elsevier Ireland Ltd.