Proyecto de comunicación de las neurociencias a través de una obra de teatro : El placer de ser hormiga

Tesis (Especialista en Comunicación Pública de la Ciencia y Periodismo Científico)--Universidad Nacional de Córdoba, Facultad de Matemática, Astronomía,Física y Computación, 2018.Especialización conjunta con la Escuela de Ciencias de la Información. Facultad de Derecho y Ciencias Sociales-UNC.Este proyecto tiene como objetivo plantear nociones básicas sobre el funcionamiento del cerebro, que sirva como anclaje para un mejor entendimiento de los avances científicos en tópicos inminentemente psicológicos y/o sociales abordados desde una mirada neurocientífica.“El placer de ser hormiga” es el título de la obra de teatro cuyo argumento vincula las neurociencias con la vida cotidiana. La obra trata acerca de líneas de investigación desarrolladas en laboratorios de Córdoba. En este caso particular el foco está puesto sobre drogas y cerebro y cómo nuestro cerebro procesa el amor y el placer. Se busca dar herramientas pedagógicas a través del arte, para abordar el estudio del sistema nervioso, las relaciones amorosas y la interacción con sustancias psicoactivas entre los adolescentes.This project aims to raise basic notions about the functioning of the brain, which serves as an anchor for a better understanding of scientific advances in imminently psychological and / or social topics approached from a neuroscientific perspective. "The pleasure of being an ant" is the title of the play whose argument links the neurosciences with everyday life. The work deals with research lines developed in laboratories in Córdoba. In this particular case the focus is on drugs and brain and how our brain processes love and pleasure. It seeks to provide pedagogical tools through art, to address the study of the nervous system, love relationships and interaction with psychoactive substances among adolescents

Acciones tróficas de GABA: implicancias en la diferenciación sexual del cerebro.

Tesis (Grado Doctor en Ciencias Biológicas)--Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Lugar de Trabajo: Laboratorio de Neurofisiología. : Instituto de Investigación Médica Mercedes y Martín Ferreyra. INIMEC-CONICET-Universidad Nacional de Córdoba. 2014 - 120 h.+ CD. ils.; tabls.; grafs. Contiene Referencia Bibliográfica. Abstract en español e inglés.GABA ejerce acciones tróficas en neuronas inmaduras a través de sus receptores GABAa. Con el objetivo de analizar diferencias sexuales en dicho efecto se estudiaron características distintivas de las neuronas hipotalámicas de machos y hembras a nivel de propiedades intrínsecas de la membrana, potencial de reversión y concentración intracelular de Cl-, sensibilidad al ligando, tipo de respuesta a moduladores específicos y la eficacia con la que éstos actúan en relación a las subunidades que componen los receptores. Algunas diferencias sexuales, como la mayor eficacia de propofol en hembras, nos habilitaron a hipotetizar la existencia de diferencias en el crecimiento y diferenciación entre machos y hembras en respuesta a la activación de los receptores GABAa. La activación crónica de los mismos provoca una reducción de la longitud axonal y un aumento de la longitud de los procesos menores en ambos sexos. El análisis de las vías intracelulares involucradas en este efecto posiciona al calcio como actor principal ya que el bloqueo farmacológico de la entrada de dicho ión es capaz de revertir la reducción de la longitud axonal. Los resultados obtenidos en este trabajo aportan nuevas evidencias sobre la participación de los receptores GABAa en el crecimiento y fisiología de neuronas hipotalámicas macho y hembra

Sex differences in GABA-mediated calcium influx in hypothalamic neurons

GABAA receptor (GABAAR) activation exerts trophic actions in immature neurons through depolarization of resting membrane potential gating the opening of voltage-dependent calcium channels. Previous results from our lab have shown gender-biased GABAAR responses in cultured hypothalamic neurons. These differences were found before brain masculinisation by gonadal hormones. Considering these, in this work we evaluated the GABAAR-mediated Ca2+ entry in cultured neurons segregated by gonadal type. Hypothalamic cells were obtained from embryonic brains at E16 (both male and female), two days before the peak of testosterone production by the foetal testis, and cultured for 2 days. To measure calcium signals, neurons were loaded with the calcium indicator Cal-520, followed by a time-lapse recording on live cells using a spinning disk microscope. Our results show that there are more male than female neurons responding to GABAAR stimulation. Additionally, almost 50% of male neurons did not recover basal calcium level after stimulation, in contrast to only 20% observed in females. Moreover, although nifedipine blocks intracellular calcium entry equally, it was stronger in males. Together, these results highlight the influence of neural sex differences irrespectively of sexual hormone exposurehttp://www.saneurociencias.org.ar/san2017-program/Fil: Mir, Franco Rafael. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Mir, Franco Rafael. Universidad Nacional de La Rioja. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Wilson, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Laboratorio de Neurobiología; Argentina.Fil: Cambiasso, María Julia. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular B; Argentina.Fil: Cambiasso, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Biología Celular, Microbiologí

Postweaning Enriched Environment Enhances Cognitive Function and Brain-Derived Neurotrophic Factor Signaling in the Hippocampus in Maternally Separated Rats

Adverse environments during early life may lead to different neurophysiological and behavioral consequences, including depression and learning and memory deficits that persist into adulthood. Previously, we demonstrated that exposure to an enriched environment during adolescence mitigates the cognitive impairment observed after maternal separation in a task-specific manner. However, underlying neural mechanisms are still not fully understood. The current study examines the effects of neonatal maternal separation (MS) and postweaning environmental enrichment (EE) on spatial learning and memory performance in a short version of the Barnes Maze, active and passive behaviors in the forced swim test, and on TrkB/BDNF receptor expression in the hippocampus. Our results revealed that MS impaired acquisition learning and that enriched rats performed better than non-enriched rats in acquisition trials, regardless of early conditions. During the probe, enriched-housed rats demonstrated better performance than those reared in standard conditions. No significant differences between groups were found in the forced swim test. Both MS and EE increase full-length TrkB expression, and the combination of MS and EE treatment caused the highest levels of this protein expression. Similarly, truncated TrkB expression was higher in the MS/EE group. Animal facility rearing (AFR) non-enriched groups present the lowest activation of phosphorylated Erk, a canonical downstream kinase of TrkB signaling. Taken together, our results demonstrate the importance of enriched environment as an intervention to ameliorate the effects of maternal separation on spatial learning and memory. TrkB/BDNF signaling could mediate neuroplastic changes related to learning and memory during exposure to enriched environment.Fil: Cordier, Javier Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; ArgentinaFil: Aguggia, Julieta Paola. 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; ArgentinaFil: Danelon, Víctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Mir, Franco Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Rioja; Argentina. Universidad Nacional de Córdoba. Facultad de Cs.exactas Físicas y Naturales. Departamento de Fisiología. Cátedra de Fisiología Animal; ArgentinaFil: Rivarola, María Angélica. 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 Cs.exactas Físicas y Naturales. Departamento de Fisiología. Cátedra de Fisiología Animal; ArgentinaFil: Masco, Daniel Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Estradiol-dependent axogenesis and Ngn3 expression are determined by XY sex chromosome complement in hypothalamic neurons

Hypothalamic neurons show sex differences in neuritogenesis, female neurons have longer axons and higher levels of the neuritogenic factor neurogenin 3 (Ngn3) than male neurons in vitro. Moreover, the effect of 17-β-estradiol (E2) on axonal growth and Ngn3 expression is only found in male-derived neurons. To investigate whether sex chromosomes regulate these early sex differences in neuritogenesis by regulating the E2 effect on Ngn3, we evaluated the growth and differentiation of hypothalamic neurons derived from the “four core genotypes” mouse model, in which the factors of “gonadal sex” and “sex chromosome complement” are dissociated. We showed that sex differences in neurite outgrowth are determined by sex chromosome complement (XX > XY). Moreover, E2 increased the mRNA expression of Ngn3 and axonal length only in XY neurons. ERα/β expressions are regulated by sex chromosome complement; however, E2-effect on Ngn3 expression in XY neurons was only fully reproduced by PPT, a specific ligand of ERα, and prevented by MPP, a specific antagonist of ERα. Together our data indicate that sex chromosomes regulate early development of hypothalamic neurons by orchestrating not only sex differences in neuritogenesis, but also regulating the effect of E2 on Ngn3 expression through activation of ERα in hypothalamic neurons.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Mir, Franco Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Scerbo, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Arevalo, María Angeles. Instituto de Salud Carlos Iii (isciii); EspañaFil: García-Segura, Luis Miguel. Instituto de Salud Carlos Iii (isciii); EspañaFil: Cambiasso, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Sex Differences in Anxiety and Depression: What Can (and Cannot) Preclinical Studies Tell Us?

In recent years, the gender perspective in scientific research and sex differences in biological studies on emotional disorders have become increasingly important. However, sex bias in basic research on anxiety and depression is still far from being covered. This review addresses the study of sex differences in the field of anxiety and depression using animal models that consider this issue so far. What can preclinical studies tell us and what are their main limitations? First, we describe the behavioral tests most frequently used in preclinical research to assess depressive-like and anxiety-like behaviors in rodents. Then, we analyze the main findings, strengths, and weaknesses of rodent models of anxiety and depression, dividing them into three main categories: sex chromosome complement-biased sex differences; gonadal hormone-biased sex differences; environmental-biased sex differences. Regardless of the animal model used, none can reproduce all the characteristics of such complex and multifactorial pathologies as anxiety and depressive disorders; however, each animal model contributes to elucidating the bases that underlie these disorders. The importance is highlighted of considering sex differences in the responses that emerge from each model