Do We Know Our Brain? A Challenge of Senses

One of the most important challenges of the current scientists is to bring their knowledge, methods, procedures, and results to the society. Education is a main resource that students have to shape their future. So, it is fundamental to create bridges between science and education, through new forms of science divulgation. The objective of this BAW project was to improve students? knowledge about the brain functioning, brain protection, and also how tobecome neuroscientist in Argentina. For that purpose, during Brain Awareness Week (BAW) in March 2018, we visited three secondary schools located in Misiones province: Instituto Roque Gonza´lez (Posadas), Instituto Madre de laMisericordia (Posadas), and Escuela Provincial de Educacion Técnica (E.P.E.T.) N° 50 (Leandro N. Alem). We developed the project through guide questions, group games, sense tests, and a final talk with a total of more than 200 students.We focused on the participation of the students: They were able to experience themselves and many questions arose during the talks, which were very dynamic and varied among the different schools. Children, together with the professors and school directors, enjoyed and took advantage of the opportunity of having neuroscientists in the schools. Teachers repeatedly thanked us for bringing our research and knowledge to very distant provinces like Misiones.This work was supported by grants of SAN (BAW); Transportes Rio Uruguay; E.P.E.T. N° 50 and G. Rosciszewski family.Fil: Rosciszewski, Gerardo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Murta, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Cadena, María Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Cieri, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaXXXIII Reunión Anual de la Sociedad Argentina de Investigación en NeurocienciasCórdobaArgentinaSociedad Argentina de Investigación en Neurociencia

Pathological Neuroinflammatory Conversion of Reactive Astrocytes Is Induced by Microglia and Involves Chromatin Remodeling

Following brain injury or in neurodegenerative diseases, astrocytes become reactive and may suffer pathological remodeling, features of which are the loss of their homeostatic functions and a pro-inflammatory gain of function that facilitates neurodegeneration. Pharmacological intervention to modulate this astroglial response and neuroinflammation is an interesting new therapeutic research strategy, but it still requires a deeper understanding of the underlying cellular and molecular mechanisms of the phenomenon. Based on the known microglial–astroglial interaction, the prominent role of the nuclear factor kappa B (NF-κB) pathway in mediating astroglial pathological pro-inflammatory gain of function, and its ability to recruit chromatin-remodeling enzymes, we first explored the microglial role in the initiation of astroglial pro-inflammatory conversion and then monitored the progression of epigenetic changes in the astrocytic chromatin. Different configurations of primary glial culture were used to modulate microglia–astrocyte crosstalk while inducing pro-inflammatory gain of function by lipopolysaccharide (LPS) exposure. In vivo, brain ischemia by cortical devascularization (pial disruption) was performed to verify the presence of epigenetic marks in reactive astrocytes. Our results showed that 1) microglia is required to initiate the pathological conversion of astrocytes by triggering the NF-κB signaling pathway; 2) this interaction is mediated by soluble factors and induces stable astroglial phenotypic changes; 3) the pathological conversion promotes chromatin remodeling with stable increase in H3K9K14ac, temporary increase in H3K27ac, and temporary reduction in heterochromatin mark H3K9me3; and 4) in vivo reactive astrocytes show increased H3K27ac mark in the neuroinflammatory milieu from the ischemic penumbra. Our findings indicate that astroglial pathological pro-inflammatory gain of function is associated with profound changes in the configuration of astrocytic chromatin, which in turn are initiated by microglia-derived cues. These results open a new avenue in the study of potential pharmacological interventions that modify the initiation and stabilization of astroglial pathological remodeling, which would be useful in acute and chronic CNS injury. Epigenetic changes represent a plausible pharmacological target to interfere with the stabilization of the pathological astroglial phenotype.Fil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Vidos, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Monteverde Busso, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Cieri, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Pathological Neuroinflammatory Conversion of Reactive Astrocytes Is Induced by Microglia and Involves Chromatin Remodeling

Following brain injury or in neurodegenerative diseases, astrocytes become reactive and may suffer pathological remodeling, features of which are the loss of their homeostatic functions and a pro-inflammatory gain of function that facilitates neurodegeneration. Pharmacological intervention to modulate this astroglial response and neuroinflammation is an interesting new therapeutic research strategy, but it still requires a deeper understanding of the underlying cellular and molecular mechanisms of the phenomenon. Based on the known microglial–astroglial interaction, the prominent role of the nuclear factor kappa B (NF-κB) pathway in mediating astroglial pathological pro-inflammatory gain of function, and its ability to recruit chromatin-remodeling enzymes, we first explored the microglial role in the initiation of astroglial pro-inflammatory conversion and then monitored the progression of epigenetic changes in the astrocytic chromatin. Different configurations of primary glial culture were used to modulate microglia–astrocyte crosstalk while inducing pro-inflammatory gain of function by lipopolysaccharide (LPS) exposure. In vivo, brain ischemia by cortical devascularization (pial disruption) was performed to verify the presence of epigenetic marks in reactive astrocytes. Our results showed that 1) microglia is required to initiate the pathological conversion of astrocytes by triggering the NF-κB signaling pathway; 2) this interaction is mediated by soluble factors and induces stable astroglial phenotypic changes; 3) the pathological conversion promotes chromatin remodeling with stable increase in H3K9K14ac, temporary increase in H3K27ac, and temporary reduction in heterochromatin mark H3K9me3; and 4) in vivo reactive astrocytes show increased H3K27ac mark in the neuroinflammatory milieu from the ischemic penumbra. Our findings indicate that astroglial pathological pro-inflammatory gain of function is associated with profound changes in the configuration of astrocytic chromatin, which in turn are initiated by microglia-derived cues. These results open a new avenue in the study of potential pharmacological interventions that modify the initiation and stabilization of astroglial pathological remodeling, which would be useful in acute and chronic CNS injury. Epigenetic changes represent a plausible pharmacological target to interfere with the stabilization of the pathological astroglial phenotype

Detrimental Effects of HMGB-1 Require Microglial-Astroglial Interaction: Implications for the Status Epilepticus -Induced Neuroinflammation

Temporal Lobe Epilepsy (TLE) is the most common form of human epilepsy and available treatments with antiepileptic drugs are not disease-modifying therapies. The neuroinflammation, neuronal death and exacerbated plasticity that occur during the silent period, following the initial precipitating event (IPE), seem to be crucial for epileptogenesis. Damage Associated Molecular Patterns (DAMP) such as HMGB-1, are released early during this period concomitantly with a phenomenon of reactive gliosis and neurodegeneration. Here, using a combination of primary neuronal and glial cell cultures, we show that exposure to HMGB-1 induces dendrite loss and neurodegeneration in a glial-dependent manner. In glial cells, loss of function studies showed that HMGB-1 exposure induces NF-κB activation by engaging a signaling pathway that involves TLR2, TLR4, and RAGE. In the absence of glial cells, HMGB-1 failed to induce neurodegeneration of primary cultured cortical neurons. Moreover, purified astrocytes were unable to fully respond to HMGB-1 with NF-κB activation and required microglial cooperation. In agreement, in vivo HMGB-1 blockage with glycyrrhizin, immediately after pilocarpine-induced status epilepticus (SE), reduced neuronal degeneration, reactive astrogliosis and microgliosis in the long term. We conclude that microglial-astroglial cooperation is required for astrocytes to respond to HMGB-1 and to induce neurodegeneration. Disruption of this HMGB-1 mediated signaling pathway shows beneficial effects by reducing neuroinflammation and neurodegeneration after SE. Thus, early treatment strategies during the latency period aimed at blocking downstream signaling pathways activated by HMGB-1 are likely to have a significant effect in the neuroinflammation and neurodegeneration that are proposed as key factors in epileptogenesis.Fil: Rosciszewski, Gerardo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Cadena, María Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Cieri, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Lukin, Jeronimo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Rossi, Alicia Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Murta, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Reines, Analia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Gomes, Flávia C. A.. Universidade Federal do Rio de Janeiro; BrasilFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Reference ranges for knee height in Argentine children and adolescents aged 2 to 18 years

Objectives: Measurement of height is essential in the anthropometric assessment of growth and nutritional status. In some conditions, height measurement may be difficult or impossible. Proxy measurement such as knee height (KH) have been proposed to predict stature in such cases, but reference percentile ranges and charts for healthy, well-nourished children are currently unavailable. This study was designed to develop sex-specific KH reference percentile ranges and charts in Argentine children ranging from 2 to 18 years of age. Methods: We collected and analyzed cross-sectional data for KH from 861 Argentine children and adolescents aged 2 to 18 years. Generalized additive models for location, scale, and shape were used to calculate semiparametric smoothed percentile reference ranges, and charts by age and sex. Linear regression and correlation analyses were performed to know the association between KH and height. Results: The new reference ranges show that KH growth rose sharply until puberty. Peak KH velocity occurs 1 year earlier than peak height velocity. At puberty KH growth decelerated rapidly in females and increased slightly until 15 years and plateaued at this age, while it had a more gradual deceleration in males up to 11 years old, later increased slightly until 17 years and plateaued at this age. The correlation coefficient between height and KH was r = 0.98 for both sexes (p <.001). Conclusions: The new reference percentile ranges for KH measures for healthy children and adolescents provide a useful growth and nutritional assessment tool in a wide variety of settings. KH has a strong agreement with stature.Fil: Ruiz Brunner, María de Las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Escuela de Nutrición; ArgentinaFil: Cuestas, María Eloisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Física Enrique Gaviola. Universidad Nacional de Córdoba. Instituto de Física Enrique Gaviola; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Cieri, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Escuela de Nutrición; ArgentinaFil: Cuestas, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Hospital Privado Universitario de Córdoba; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentin

Progression of reactive gliosis and astroglial phenotypic changes following stab wound-induced traumatic brain injury in mice

Astrocytes are the main homeostatic cells in the central nervous system (CNS) and they have an essential role in preserving neuronal physiology. After brain injury, astrocytes become reactive, and that involves a profound change in the astroglial gene expression program as well as intense cytoskeleton remodeling that has been classically shown by the up-regulation of glial fibrillary acidic protein (GFAP), a pan-reactive gene over-expressed in reactive astrocytes, independently of the type of injury. Using the stab wound rodent model of penetrating traumatic injury in the cortex, we here studied the reactive astroglial morphology and reactive microgliosis in detail at 1, 3, 7, 14, and 28 days post-injury (dpi). By combining immunohistochemistry, morphometrical parameters, and Sholl analysis, we segmented the astroglial cell population into clusters of reactive astrocytes that were localized in the core, penumbra, and distal regions of the stab wound. Specifically, highly reactive clusters with more complex morphology, increased C3, decreased aquaporin-4 (AQP4), and glutamine synthetase (GS) expression, were enriched at 7 dpi when behavioral alterations, microgliosis, and neuronal alterations in injured mice were most significant. While pro-inflammatory gain of function with peripheral lipopolysaccharide (LPS) administration immediately after a stab wound expanded these highly reactive astroglial clusters, the treatment with the NF-κB inhibitor sulfasalazine reduced the abundance of this highly reactive cluster. Increased neuronal loss and exacerbated reactive microgliosis at 7 dpi were associated with the expansion of the highly reactive astroglial cluster. We conclude that highly reactive astrocytes found in stab wound injury, but expanded in pro-inflammatory conditions, are a population of astrocytes that become engaged in pathological remodeling with a pro-inflammatory gain of function and loss of homeostatic capacity. Controlling this astroglial population may be a tempting strategy to reduce neuronal loss and neuroinflammation in the injured brain.Fil: Cieri, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Gomez Cuautle, Dante Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Mailing, Ingrid Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin