The Complex Interactions Between Obesity, Metabolism and the Brain

Obesity is increasing at unprecedented levels globally, and the overall impact of obesity on the various organ systems of the body is only beginning to be fully appreciated. Because of the myriad of direct and indirect effects of obesity causing dysfunction of multiple tissues and organs, it is likely that there will be heterogeneity in the presentation of obesity effects in any given population. Taken together, these realities make it increasingly difficult to understand the complex interplay between obesity effects on different organs, including the brain. The focus of this review is to provide a comprehensive view of metabolic disturbances present in obesity, their direct and indirect effects on the different organ systems of the body, and to discuss the interaction of these effects in the context of brain aging and the development of neurodegenerative diseases

Mujer y discapacidad

La mujer frente a la discapacidad forma parte de una realidad donde, entre otros factores, el género es uno de los que sobresalen negativamente. En un escenario donde la desigualdad y la inequidad siguen ejerciendo un efecto negativo en la mujer, se suma la carencia de Programas de Atención Primaria de la Salud, esencialmente en los servicios de Salud Sexual y Reproductiva. Las barreras enumeradas, junto a la inaccesibilidad dada por múltiples factores que constituyen una limitante, hacen que las políticas de salud deban ser necesariamente replanteadas.Facultad de Ciencias Médica

Adenovirus-mediated suppression of hypothalamic glucokinase affects feeding behavior

Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-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 Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad de Concepción; ChileFil: Millán, Carola. Universidad de Concepción; Chile. Universidad Adolfo Ibañez; ChileFil: Barahona, María José. Universidad de Concepción; ChileFil: Recabal, Antonia. Universidad de Concepción; ChileFil: Salgado, Magdiel. Universidad de Concepción; ChileFil: Martinez, Fernando. Universidad de Concepción; ChileFil: Ordenes, Patricio. Universidad de Concepción; ChileFil: Elizondo Vega, Roberto. Universidad de Concepción; ChileFil: Sepúlveda, Fernando. Universidad de Concepción; ChileFil: Uribe, Elena. Universidad de Concepción; ChileFil: García Robles, María de los Ángeles. Universidad de Concepción; Chil

MCT Expression and Lactate Influx/Efflux in Tanycytes Involved in Glia-Neuron Metabolic Interaction

Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V) tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs) in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes

Aprendizajes y prácticas educativas en las actuales condiciones de época: COVID-19

“Esta obra colectiva es el resultado de una convocatoria a docentes, investigadores y profesionales del campo pedagógico a visibilizar procesos investigativos y prácticas educativas situadas en el marco de COVI-19. La misma se inscribe en el trabajo llevado a cabo por el equipo de Investigación responsable del Proyecto “Sentidos y significados acerca de aprender en las actuales condiciones de época: un estudio con docentes y estudiantes de la educación secundarias en la ciudad de Córdoba” de la Facultad de Filosofía y Humanidades. Universidad Nacional de Córdoba. El momento excepcional que estamos atravesando, pero que también nos atraviesa, ha modificado la percepción temporal a punto tal que habitamos un tiempo acelerado y angustiante que nos exige la producción de conocimiento provisorio. La presente publicación 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 encontrarán pluralidad de voces acerca de enseñar y aprender durante la pandemia. Este texto es una pausa para reflexionar sobre el hacer y las prácticas educativas por venir”.Fil: Beltramino, Lucia (comp.). Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Archivología; Argentina

Unraveling the Burden of Iron in Neurodegeneration: Intersections with Amyloid Beta Peptide Pathology

Iron overload is a hallmark of many neurodegenerative processes such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Unbound iron accumulated as a consequence of brain aging is highly reactive with water and oxygen and produces reactive oxygen species (ROS) or free radicals. ROS are toxic compounds able to damage cell membranes, DNA, and mitochondria. Which are the mechanisms involved in neuronal iron homeostasis and in neuronal response to iron-induced oxidative stress constitutes a cutting-edge topic in metalloneurobiology. Increasing our knowledge about the underlying mechanisms that operate in iron accumulation and their consequences would shed light on the comprehension of the molecular events that participate in the pathophysiology of the abovementioned neurodegenerative diseases. In this review, current evidences about iron accumulation in the brain, the signaling mechanisms triggered by metal overload, as well as the interaction between amyloid β (Aβ) and iron, will be summarized

α,25(OH)2D3 promotes oxidative stress in endothelial cells transformed by vGPCR

The infectious cause of Kaposi’s sarcoma (KS) neoplasm is KS-associated Herpesvirus (KSHV or human herpesvirus 8). Furthermore, virally G Protein-coupled Receptor (vGPCR) is one of the molecules from the lytic phase able to induce KS-associated cellular modifications through paracrine oncogenesis. We have previously demonstrated that 1α,25(OH)2D3 exerts antiproliferative effects on endothelial cells that stably express vGPCR by inhibiting NF-κB pathway and promoting apoptosis and autophagy. Oxidative stress is frequent in many types of cancer where reactive oxygen species (ROS) can act as a promoting or suppressing agent. In this work, our goal was to study the involvement of ROS as part of the antineoplastic mechanisms triggered by 1α,25(OH)2D3 in vGPCR cells. By a spectrofluorimetric method using the H2-DCF-DA probe, ROS levels were detected higher than control conditions after 1α,25(OH)2D3 (10 nM, 24 or 48 h) treatment. When VDR expression was knocked down by shRNA against VDR (vGPCR-shVDR cell line), ROS increase was found to be VDR dependent (48 h). Our previous reports indicated that vGPCR cells proliferation decreases at 80% after 1α,25(OH)2D3 treatment, triggering cell cycle arrest and apoptosis by a mechanism dependent on the caspase-3 cleavage. In this case, Western blot studies showed an increase expression of pro-apoptotic proteins like BIM and caspase-3 cleavage by 1α,25(OH)2D3 (10 nM, 48 h) and no reversal effect by N-Acetyl-cysteine (1 mM) antioxidant was observed. Altogether, these preliminary results suggest that ROS levels promotion by 1α,25(OH)2D3 through VDR, triggers apoptosis-related mechanisms on vGPCR cells.Fil: Tapia, Cinthya Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaLVI Annual Meeting Argentine Society for Biochemistry and Molecular Biology and XV Annual Meeting Argentinean Society for General MicrobiologyArgentinaSociedad Argentina de Investigación BioquímicaAsociación Civil de Microbiología Genera

In vitro 6-hydroxydopamine-induced neurotoxicity: New insights on NFκB modulation

Neuronal exposure to 6-hydroxydopamine (6-OHDA), a hydroxylated analog of dopamine, constitutes a very useful strategy for studying the molecular events associated with neuronal death in Parkinson's disease. 6-OHDA increases oxidant levels and impairs mitochondrial respiratory chain, thus promoting neuronal injury and death. Despite the extensive use of 6-OHDA in animal models, the exact molecular events triggered by this neurotoxicant at the neuronal level have not been yet fully understood. Human IMR-32 neuroblastoma cells exposed to increasing concentrations of 6-OHDA displayed high levels of reactive oxygen species and increased plasma membrane permeability with concomitant cell viability diminution. As part of the neuronal response to 6-OHDA exposure, the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) p65 subunit was observed. NFκB nuclear localization was also accompanied by an increase of IκB phosphorylation as well as a rise in cyclooxygenase-2 (COX-2) and the prostaglandin receptor, EP4, mRNA levels. Even though the canonical pathways participating in the modulation of NFκB have been extensively described, here we tested the hypothesis that 6-OHDA-induced injury can activate lipid signaling and, in turn, modulate the transcriptional response. 6-OHDA challenge triggered the activation of lipid signaling pathways and increased phosphatidic acid (PA), diacylglycerol and free fatty acid levels in human neuroblastoma cells. The inhibition of PA production was able to prevent the decrease in cell viability triggered by 6-OHDA, the nuclear translocation of NFκB p65 subunit and the rise in COX-2 mRNA expression. Our results indicate that the onset of the inflammatory process triggered by 6-OHDA involves the activation of PA signaling that, in turn, governs NFκB subcellular localization and COX-2 expression.Fil: Iglesias González, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Conde, Melisa Ailén. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: González Pardo, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Uranga, Romina Maria. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin