29 research outputs found
The complex interactions between obesity, metabolism and the brain
Obesity is increasing at unprecedented levels globally, and the overall impact ofobesity on the various organ systems of the body is only beginning to be fullyappreciated. Because of the myriad of direct and indirect effects of obesity causingdysfunction of multiple tissues and organs, it is likely that there will be heterogeneityin the presentation of obesity effects in any given population. Taken together, theserealities make it increasingly difficult to understand the complex interplay betweenobesity effects on different organs, including the brain. The focus of this review isto provide a comprehensive view of metabolic disturbances present in obesity, theirdirect and indirect effects on the different organ systems of the body, and to discussthe interaction of these effects in the context of brain aging and the development ofneurodegenerative diseases.Fil: Uranga, Romina Maria. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Keller, Jeffrey Neil. Louisiana State University System; Estados Unido
Iron-Induced Oxidative Injury Differentially Regulates PI3K/Akt/GSK3ÎČ Pathway in Synaptic Endings from Adult and Aged Rats
In this work we study the state of phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK3 beta) signaling during oxidative injury triggered by free iron using cerebral cortex synaptic endings isolated from adult (4-month-old) and aged (28-month-old) rats. Synaptosomes were exposed to FeSO4 (50 microM) for different periods of time and synaptosomal viability and the state of the PI3K/Akt/GSK3 beta pathway were evaluated in adult and aged animals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage were significantly affected in both age groups. However, aged animals showed a greater susceptibility to oxidative stress. In adults, Akt was activated after a brief exposure time (5 min), whereas in aged animals activation occurred after 5 and 30 min of incubation with the metal ion. GSK3 beta phosphorylation showed the same activation pattern as that observed for Akt. Both Akt and GSK3 beta phosphorylation were dependent on PI3K activation. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation was temporally coincident with Akt activation and was PI3K dependent in adults, whereas ERK1/2 activation in aged rats was higher than that observed in adults and showed no dependence on PI3K activity. We demonstrate here that synaptic endings from adult and aged animals subjected to iron-induced neurotoxicity show a differential profile in the activation of PI3K/Akt/GSK3 beta. Our results strongly suggest that the increased susceptibility of aged animals to oxidative injury provokes a differential modulation of key signaling pathways involved in synaptic plasticity and neuronal survivalFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Giusto, Norma Maria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentin
Enhanced phosphatidylinositol 3-kinase (PI3K)/Akt signaling has pleiotropic targets in hippocampal neurons exposed to iron-induced oxidative stress
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a key component in synaptic plasticity and neuronal survival. The aim of this work was to investigate the participation of the PI3K/Akt pathway and its outcome on different molecular targets such as glycogen synthase kinase 3ÎČ (GSK3ÎČ) and Forkhead box-O (FoxO) transcription factors during mild oxidative stress triggered by iron overload. The exposure of mouse hippocampal neurons (HT22) to different concentrations of Fe 2+ (25-200 ÎŒM) for 24 h led us to define a mild oxidative injury status (50 ÎŒM Fe 2+ ) in which cell morphology showed changes typical of neuronal damage, with increased lipid peroxidation and cellular oxidant levels but no alteration of cellular viability. There was a simultaneous increase in both Akt and GSK3ÎČ phosphorylation. Levels of phospho-FoxO3a (inactive form) increased in the cytosolic fraction of cells treated with iron in a PI3K-dependent manner. Moreover, PI3K and Akt translocated to the nucleus in response to oxidative stress. Iron-overloaded cells harboring a constitutively active form of Akt showed decreased oxidants levels. Indeed, glutathione (GSH) synthesis under oxidative stress conditions was regulated by activated Akt. Our results show that activation of the PI3K/Akt pathway during iron-induced neurotoxicity regulates multiple targets such as GSK3ÎČ, FoxO transcriptional activity and glutathione metabolism thus modulating neuronal response to oxidative stress.Fil: Uranga, Romina Maria. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CONICET BahĂa Blanca. Instituto de Investigaciones BioquĂmicas BahĂa Blanca (i); ArgentinaFil: Katz, Sebastian. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CONICET BahĂa Blanca. Instituto de Investigaciones BioquĂmicas BahĂa Blanca (i); ArgentinaFil: Salvador, Gabriela Alejandra. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CONICET BahĂa Blanca. Instituto de Investigaciones BioquĂmicas BahĂa Blanca (i); Argentin
Lipids at the crossroad of α-synuclein function and dysfunction: Biological and pathological implications
Since its discovery, the study of the biological role ofα-synuclein and its pathologicalimplications has been the subject of increasing interest. The propensity to adoptdifferent conformational states governing its aggregation and fibrillation makes thissmall 14-kDa cytosolic protein one of the main etiologic factors associated withdegenerative disorders known as synucleinopathies. The structure, function, and toxicityofα-synuclein and the possibility of different therapeutic approaches to target theprotein have been extensively investigated and reviewed. One intriguing characteristic ofα-synuclein is the different ways in which it interacts with lipids. Though in-depth studieshave been carried out in this field, the information they have produced is puzzling andthe precise role of lipids inα-synuclein biology and pathology andvice versais still largelyunknown. Here we provide an overview and discussion of the main findings relating toα-synuclein/lipid interaction and its involvement in the modulation of lipid metabolismand signaling.Fil: Alza, Natalia Paola. Universidad Nacional del Sur. Departamento de QuĂmica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Iglesias GonzĂĄlez, Pablo AndrĂ©s. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Conde, Melisa AilĂ©n. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Salvador, Gabriela Alejandra. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentin
Selective vulnerability of neurons to acute toxicity after proteasome inhibitor treatment: Implications for oxidative stress and insolubility of newly synthesized proteins
Maintaining protein homeostasis is vital to cell viability, with numerous studies demonstrating a role for proteasome inhibition occurring during the aging of a variety of tissues and, presumably, contributing to the disruption of cellular homeostasis during aging. In this study we sought to elucidate the differences between neurons and astrocytes in regard to basal levels of protein synthesis, proteasome-mediated protein degradation, and sensitivity to cytotoxicity after proteasome inhibitor treatment. In these studies we demonstrate that neurons have an increased vulnerability, compared to astrocyte cultures, to proteasome-inhibitor-induced cytotoxicity. No significant difference was observed between these two cell types in regard to the basal rates of protein synthesis, or basal rates of protein degradation, in the pool of short-lived proteins. After proteasome inhibitor treatment neuronal crude lysates were observed to undergo greater increases in the levels of ubiquitinated and oxidized proteins and selectively exhibited increased levels of newly synthesized proteins accumulating within the insoluble protein pool, compared to astrocytes. Together, these data suggest a role for increased oxidized proteins and sequestration of newly synthesized proteins in the insoluble protein pool, as potential mediators of the selective neurotoxicity after proteasome inhibitor treatment. The implications for neurons exhibiting increased sensitivity to acute proteasome inhibitor exposure, and the corresponding changes in protein homeostasis observed after proteasome inhibition, are discussed in the context of both aging and age-related disorders of the nervous system.Fil: Dasuri, Kalavathi. State University of Louisiana; Estados UnidosFil: Ebenezer, Philip J.. State University of Louisiana; Estados UnidosFil: Zhang, Le. State University of Louisiana; Estados UnidosFil: Fernandez Kim, Sun Ok. State University of Louisiana; Estados UnidosFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: GavilĂĄn, Elena. State University of Louisiana; Estados UnidosFil: Di Blasio, Alessia. State University of Louisiana; Estados UnidosFil: Keller, Jeffrey N.. State University of Louisiana; Estados Unido
Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior
Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic ÎČ-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons. In this study, we developed an adenovirus expressing GK shRNA to inhibit GK expression in vivo. When injected into the 3V of rats, this adenovirus preferentially transduced tanycytes. qRT-PCR and Western blot assays confirmed GK mRNA and protein levels were lower in GK knockdown animals compared to the controls. In response to an intracerebroventricular glucose injection, the mRNA levels of anorexigenic POMC and CART and orexigenic AgRP and NPY neuropeptides were altered in GK knockdown animals. Similarly, food intake, meal duration, frequency of eating events and the cumulative eating time were increased, whereas the intervals between meals were decreased in GK knockdown rats, suggesting a decrease in satiety. Thus, GK expression in the ventricular cells appears to play an important role in feeding behavior.Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad de ConcepciĂłn; ChileFil: MillĂĄn, Carola. Universidad de ConcepciĂłn; Chile. Universidad Adolfo Ibañez; ChileFil: Barahona, MarĂa JosĂ©. Universidad de ConcepciĂłn; ChileFil: Recabal, Antonia. Universidad de ConcepciĂłn; ChileFil: Salgado, Magdiel. Universidad de ConcepciĂłn; ChileFil: Martinez, Fernando. Universidad de ConcepciĂłn; ChileFil: Ordenes, Patricio. Universidad de ConcepciĂłn; ChileFil: Elizondo Vega, Roberto. Universidad de ConcepciĂłn; ChileFil: SepĂșlveda, Fernando. Universidad de ConcepciĂłn; ChileFil: Uribe, Elena. Universidad de ConcepciĂłn; ChileFil: GarcĂa Robles, MarĂa de los Ăngeles. Universidad de ConcepciĂłn; Chil
Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: Implications for protein misfolding and TDP-43 regulation
Amino acid analogs promote translational errors that result in aberrant protein synthesis, and have been used to understand the effects of protein misfolding in a variety of physiological and pathological settings. TDP-43 is a protein that is linked to protein aggregation and toxicity in a variety of neurodegenerative diseases. In this study we exposed primary rat neurons and astrocyte cultures to established amino acid analogs (Canavanine and Azetidine-2-carboxylic acid), and observed both cell types undergo a dose-dependent increase in toxicity, with neurons exhibiting a greater degree of toxicity as compared to astrocytes. Neurons and astrocytes exhibited similar increases in ubiquitinated and oxidized protein following analog treatment. Analog treatment increased Heat shock protein (Hsp) levels in both neurons and astrocytes. In neurons, and to a lesser extent astrocytes, the levels of TDP-43 increased in response to analog treatment. Taken together, these data indicate that neurons exhibit preferential toxicity and alterations in TDP-43, in response to increased protein misfolding, as compared to astrocytes.Fil: Dasuri, Kalavathi. State University Of Louisiana; Estados UnidosFil: Ebenezer, Philip J.. State University Of Louisiana; Estados UnidosFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Cientificas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Bahia Blanca. Instituto de Investigaciones BioquĂmicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Gavilan, Elena. Universidad de Sevilla; EspañaFil: Zhang, Le. State University Of Louisiana; Estados UnidosFil: Fernandez-Kim, Sun O. K.. State University Of Louisiana; Estados UnidosFil: Bruce Keller, Annadora J.. State University Of Louisiana; Estados UnidosFil: Keller, Jeffrey N.. State University Of Louisiana; Estados Unido
α-Synuclein attenuates maneb neurotoxicity through the modulation of redox-sensitive transcription factors
The accumulation and aggregation of α-synuclein is a pathognomonic sign of Parkinson's disease (PD). Maneb (MB) exposure has also been reported as one environmental triggering factor of this multifactorial neurodegenerative disease. In our laboratory, we have previously reported that mild overexpression of α-synuclein (200% increase with respect to endogenous neuronal levels) can confer neuroprotection against several insults. Here, we tested the hypothesis that α-synuclein can modulate the neuronal response against MB-induced neurotoxicity. When exposed to MB, cells with endogenous α-synuclein expression displayed increased reactive oxygen species (ROS) associated with diminished glutamate-cysteine ligase catalytic subunit (GCLc) and hemeoxygenase-1 (HO-1) mRNA expressions and upregulation of the nuclear factor erythroid 2-related factor 2 (NRF2) repressor, BTB domain and CNC homolog 1 (BACH1). We found that α-synuclein overexpression (wt α-syn cells) attenuated MB-induced neuronal damage by reducing oxidative stress. Decreased ROS found in MB-treated wt α-syn cells was associated with unaltered GCLc and HO-1 mRNA expressions and decreased BACH1 expression. In addition, the increased SOD2 expression and catalase activity were associated with forkhead box O 3a (FOXO3a) nuclear compartmentalization. Cytoprotective effects observed in wt α-syn cells were also associated with the upregulation of silent information regulator 1 (SIRT1). In control cells, MB-treatment downregulated glutathione peroxidase 4 mRNA levels, which was coincident with increased ROS content, lipid peroxidation, and mitochondrial alterations. These deleterious effects were prevented by ferrostatin-1, an inhibitor of ferroptosis, under conditions of endogenous α-synuclein expression. The overexpression of α-synuclein attenuated MB toxicity by the activation of the same mechanisms as ferrostatin-1. Overall, our findings suggest that mild overexpression of α-synuclein attenuates MB-induced neurotoxicity through the modulation of NRF2 and FOXO3a transcription factors and prevents cell death probably by intervening in mechanisms associated with ferroptosis. Thus, we postulate that early stages of α-synuclein overexpression could be potentially neuroprotective against MB neurotoxicity.Fil: Conde, Melisa AilĂ©n. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂa, BioquĂmica y Farmacia; ArgentinaFil: Alza, Natalia Paola. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de QuĂmica; ArgentinaFil: Funk, Melania Iara. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de QuĂmica; ArgentinaFil: Maniscalchi VelĂĄsquez, Athina del Valle. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Benzi Juncos, Oriana Nicole. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de QuĂmica; ArgentinaFil: BergĂ©, Ignacio. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de QuĂmica; ArgentinaFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de QuĂmica; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; Argentina. Universidad Nacional del Sur. Departamento de QuĂmica; Argentin
Aprendizajes y prĂĄcticas educativas en las actuales condiciones de Ă©poca: COVID-19
âEsta obra colectiva es el resultado de una convocatoria a docentes, investigadores y profesionales del campo pedagĂłgico a visibilizar procesos investigativos y prĂĄcticas educativas situadas en el marco de COVI-19. La misma se inscribe en el trabajo llevado a cabo por el equipo de InvestigaciĂłn responsable del Proyecto âSentidos y significados acerca de aprender en las actuales condiciones de Ă©poca: un estudio con docentes y estudiantes de la educaciĂłn secundarias en la ciudad de CĂłrdobaâ de la Facultad de FilosofĂa y Humanidades. Universidad Nacional de CĂłrdoba.
El momento excepcional que estamos atravesando, pero que tambiĂ©n nos atraviesa, ha modificado la percepciĂłn temporal a punto tal que habitamos un tiempo acelerado y angustiante que nos exige la producciĂłn de conocimiento provisorio. La presente publicaciĂłn surge como un espacio para detenernos a documentar lo que nos acontece y, a su vez, como oportunidad para atesorar y resguardar las experiencias educativas que hemos construido, inventado y reinventando en este contexto. En ella encontrarĂĄn pluralidad de voces acerca de enseñar y aprender durante la pandemia. Este texto es una pausa para reflexionar sobre el hacer y las prĂĄcticas educativas por venirâ.Fil: Beltramino, Lucia (comp.). Universidad Nacional de CĂłrdoba. Facultad de FilosofĂa y Humanidades. Escuela de ArchivologĂa; Argentina
Hippocampal neuronal response to amyloid ÎČ peptide oligomers. Biological and biophysical insights
We have previously demonstrated that oligomeric amyloid ÎČ peptide (oAÎČ), known as the most harmful species of AÎČ, concomitant with iron overload led to synaptic injury and local activation of several signaling cascades. In this work, we characterized hippocampal neuronal response to oAÎČ exposure both in the presence and absence of iron. HT22 neurons exposed to iron overload displayed increased lipid peroxidation, slight loss of mitochondrial function, and activation of ERK and Akt pathways. oAÎČ neither induced an increase in lipid peroxidation nor altered mitochondrial function. However, oAÎČ alone triggered the activation of ERK and Akt, and the coincubation with oAÎČ/iron restored pAkt and pERK to the control levels. In addition, we also studied the effect of iron, oAÎČ and both conditions together, on the biophysical state of the plasma membrane by measuring the generalized polarization of the fluorescence probe Laurdan and the fluorescence anisotropy of DPH and TMA-DPH. Both studies showed that the presence of iron (even at the highest concentration tested), oAÎČ, or both conditions together, did not perturb the lipid order of the membrane. We conclude that oAÎČ activates signaling pathways in the absence of oxidative stress or membrane disturbances in hippocampal neurons.Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂmicas de BahĂa Blanca; ArgentinaL ReuniĂłn Anual de la Sociedad Argentina de InvestigaciĂłn en BioquĂmica y BiologĂa MolecularRosarioArgentinaSociedad Argentina de InvestigaciĂłn en BioquĂmica y BiologĂa Molecula