Papel de la Neurogenina 3 en las acciones neuritogénicas del estradiol en el hipocampo

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología. Fecha de lectura: 12-12-2016Las hormonas sexuales esteroideas tales como el estradiol o la testosterona, son capaces de activar en el sisteman nervioso central rutas de señalización que van a estar implicadas en procesos tales como neuritogénesis, plasticidad neuronal, neuroprotección o diferenciación sexual del cerebro. Estudios previos han mostrado que la Neurogenina 3 (Ngn 3) es un factor neuritogénico en el sistema nervioso central, en regiones como el hipocampo y el hipotálamo. Puesto que el estradiol también promueve neuritogénesis en dichas áreas, en este estudio hemos investigado si la Ngn 3 participa en las acciones neuritogénicas del estradiol. En neuronas de hipocampo en cultivos no sexados, el estradiol incrementó la neuritogénesis y la expresión transcripcional de la Ngn 3. Además, modificó la localización citoplasmática de la proteína. Dichos procesos ocurren mediante la activación del recientemente descubierto G Protein-Coupled Estrogen Receptor 1 (GPER) así como de la PI3K y Akt. Por otro lado, el silenciamiento de dicho gen in vitro abolió el efecto neuritogénico del estradiol. En cultivos sexados, observamos que las neuronas hipocampales de hembras presentan un mayor desarrollo, así como niveles superiores de expresión de Ngn 3 que las neuronas de machos. El tratamiento con testosterona y estradiol incrementó la neuritogénesis, y los niveles de ARNm de la Ngn 3 en machos, pero no en hembras. Utilizando agonistas y antagonistas de los receptores de estrógenos y andrógenos, así como inhibidores de enzimas específicas de la esteroidogénesis, hemos podido observar que las diferencias sexuales en la regulación de la transcripción de la Ngn 3 y la neuritogénesis, están moduladas por una distinta contribución de estradiol, testosterona, así como de receptores de estrógeno y andrógenos. Estos resultados sugieren que hormonas, neuroesteroides y sus correspondientes receptores participan en la regulación transcripcional de la Ngn 3 y neuritogénesis hipocampal, activando distintos programas de desarrollo en machos y hembras

Notch/neurogenin 3 signalling is involved in the neuritogenic actions of oestradiol in developing hippocampal neurones

10 pages. - PMID: 21251092 [PubMed - in process]The ovarian hormone oestradiol promotes neuritic outgrowth in different neuronal types, by mechanisms that remain elusive. Recent studies have shown that the Notch-regulated transcription factor neurogenin 3 controls neuritogenesis. In the present study, we assessed whether oestradiol regulates neurogenin 3 in primary hippocampal neurones. As expected, neuritogenesis was increased in the cultures treated with oestradiol. However, the neuritogenic action of oestradiol was not prevented by ICI 182,780, an antagonist of classical oestrogen receptors (ERs). Oestradiol decreased the expression of Hairy and Enhancer of Split-1, a Notch-regulated gene that negatively controls the expression on neurogenin 3. Furthermore, oestradiol increased the expression of neurogenin 3 and regulated its distribution between the neuronal cell nucleus and the cytoplasm. The effect of oestradiol on neurogenin 3 expression was not blocked by antagonists of classical nuclear ER-mediated transcription and was not imitated by selective agonists of nuclear ERs. By contrast, G1, a ligand of G protein receptor 30/G protein-coupled ER, fully reproduced the effect of oestradiol on neuritogenesis, neurogenin 3 expression and neurogenin 3 subcellular localisation. Moreover, knockdown of neurogenin 3 in neurones by transfection with small interference RNA for neurogenin 3 completely abrogated the neuritogenic actions of oestradiol and G1. These results suggest that oestradiol regulates neurogenin 3 in primary hippocampal neurones by a nonclassical steroid signalling mechanism, which involves the down-regulation of Notch activity and the activation of G protein receptor 30/G protein-coupled ER or of other unknown G1 targets. In addition, our findings indicate that neurogenin 3 participates in the neuritogenic mechanisms of oestradiol in hippocampal neurones.Peer reviewe

Dissolved CH4 coupled to photosynthetic picoeukaryotes in oxic waters and to cumulative chlorophyll a in anoxic waters of reservoirs

Methane (CH4) emissions from reservoirs are responsible for most of the atmospheric climatic forcing of these aquatic ecosystems, comparable to emissions from paddies or biomass burning. Primarily, CH4 is produced during the anaerobic mineralization of organic carbon in anoxic sediments by methanogenic archaea. However, the origin of the recurrent and ubiquitous CH4 supersaturation in oxic waters (i.e., the methane paradox) is still controversial. Here, we determined the dissolved CH4 concentration in the water column of 12 reservoirs during summer stratification and winter mixing to explore CH4 sources in oxic waters. Reservoir sizes ranged from 1.18 to 26.13 km(2). We found that dissolved CH4 in the water column varied by up to 4 orders of magnitude (0.02-213.64 mu mol L-1), and all oxic depths were consistently supersaturated in both periods. Phytoplanktonic sources appear to determine the concentration of CH4 in these reservoirs primarily. In anoxic waters, the depth-cumulative chlorophyll a concentration, a proxy for the phytoplanktonic biomass exported to sediments, was correlated to CH4 concentration. In oxic waters, the photosynthetic picoeukaryotes' abundance was significantly correlated to the dissolved CH4 concentration during both the stratification and the mixing. The mean depth of the reservoirs, as a surrogate of the vertical CH4 transport from sediment to the oxic waters, also contributed notably to the CH4 concentration in oxic waters. Our findings suggest that photosynthetic picoeukaryotes can play a significant role in determining CH4 concentration in oxic waters, although their role as CH4 sources to explain the methane paradox has been poorly explored

Kif21B mediates the effect of estradiol on the morphological plasticity of mouse hippocampal neurons

IntroductionNeurons are polarized cells, and their ability to change their morphology has a functional implication in the development and plasticity of the nervous system in order to establish new connections. Extracellular factors strongly influence neuronal shape and connectivity. For instance, the developmental actions of estradiol on hippocampal neurons are well characterized, and we have demonstrated in previous studies that Ngn3 mediates these actions. On the other hand, Kif21B regulates microtubule dynamics and carries out retrograde transport of the TrkB/brain-derived neurotrophic factor (BDNF) complex, essential for neuronal development.MethodsIn the present study, we assessed the involvement of kinesin Kif21B in the estradiol-dependent signaling mechanisms to regulate neuritogenesis through cultured mouse hippocampal neurons.ResultsWe show that estradiol treatment increases BDNF expression, and estradiol and BDNF modify neuron morphology through TrkB signaling. Treatment with K252a, a TrkB inhibitor, decreases dendrite branching without affecting axonal length, whereas. Combined with estradiol or BDNF, it blocks their effects on axons but not dendrites. Notably, the downregulation of Kif21B abolishes the actions of estradiol and BDNF in both the axon and dendrites. In addition, Kif21B silencing also decreases Ngn3 expression, and downregulation of Ngn3 blocks the effect of BDNF on neuron morphology.DiscussionThese results suggest that Kif21B is required for the effects of estradiol and BDNF on neuronal morphology, but phosphorylation-mediated activation of TrkB is essential only for axonal growth. Our results show that the Estradiol/BDNF/TrkB/Kif21B/Ngn3 is a new and essential pathway mediating hippocampal neuron development

Estradiol Meets Notch Signaling in Developing Neurons

The transmembrane receptor Notch, a master developmental regulator, controls gliogenesis, neurogenesis, and neurite development in the nervous system. Estradiol, acting as a hormonal signal or as a neurosteroid, also regulates these developmental processes. Here we review recent evidence indicating that estradiol and Notch signaling interact in developing hippocampal neurons by a mechanism involving the putative membrane receptor G protein-coupled receptor 30. This interaction is relevant for the control of neuronal differentiation, since the downregulation of Notch signaling by estradiol results in the upregulation of neurogenin 3, which in turn promotes dendritogenesis

Active methodologies and teaching performance: a necessary relationship in the field of education

[EN] In the present communication, we present the project developed within the Teaching Innovation Group (APAC) of the Faculty of Education at the University of Burgos: “Active Methodologies and Teacher Performance: a road towards inclusion in the classroom”. The principal objective of this project is to contribute empirical evidence on the impact that the use of active methodologies has on teaching performance in the classroom. Its results are the basis for the transformation of initial teacher training, because Universities are responsible for training the teachers who will be at the forefront of schools in the 21st c. They have therefore to be offered access to the resources in their initial and lifelong education that permit change, allowing them to construct the paradigm of inclusive, sustainable, and quality education.[ES] En la presente comunicación, presentamos el proyecto desarrollado dentro del Grupo de Innovación Docente (APAC) de la Facultad de Educación de la Universidad de Burgos: "Metodologías Activas y Desempeño Docente: un camino hacia la inclusión en el aula". El objetivo principal de este proyecto es aportar evidencia empírica sobre el impacto que tiene el uso de metodologías activas en el rendimiento docente en el aula. Sus resultados son la base para la transformación de la formación inicial del profesorado, porque las universidades son responsables de la formación de los profesores que estarán a la vanguardia de las escuelas en el 21 stdo. Por lo tanto, se les debe ofrecer acceso a los recursos en su educación inicial y de por vida que permitan el cambio, permitiéndoles construir el paradigma de la educación inclusiva, sostenible y de calidad.http://ocs.editorial.upv.es/index.php/HEAD/HEAD18Luis, MI.; De La Torre Cruz, T.; Huelmo, J.; Llamazares, MC.; Ruiz, E.; Prieto, C.; Palmero, C.... (2018). Active methodologies and teaching performance: a necessary relationship in the field of education. Editorial Universitat Politècnica de València. 995-1001. https://doi.org/10.4995/HEAD18.2018.8134OCS995100

Ergonomía y actividad física en mayores

La mayor parte de las lesiones que se producen por la realización de una actividad física reglada se deben a una falta de asesoramiento tanto en la ejecución de la actividad como en el uso de los aparatos necesarios para cada actividad. Mientras que el asesoramiento de la ejecución es responsabilidad de los profesionales a cargo en los centros de actividad física, el uso del aparato se puede ver dificultado por una falta de ergonomía en el diseño de éste. Cada vez con mayor frecuencia, las marcas de material deportivo procuran incluir partes móviles y ajustables en sus máquinas para facilitar su adecuación a las características del mayor número de usuarios posibles. Sin embargo, estos reglajes suelen resultar inválidos para las características de las personas mayores, impidiendo la práctica a un colectivo cada vez más demandante de este tipo de actividades. La presente investigación busca conocer las variables moduladoras en la percepción de las personas mayores sobre la ergonomía en su ejercicio físico, a la vez que establecer un patrón de investigación sobre el caso. Considerando los aspectos estructurales y funcionales de los gimnasios y de las personas mayores, tomamos una muestra de sujetos mayores de 55 años a los que se les administra un cuestionario ad hoc para conocer si las percepciones difieren en función de la edad del participantes, la frecuencia de la realización de la actividad o de la calidad ergonómica de los recursos e instalaciones donde se realiza la actividad física. El presente artículo muestra el proceso de validación de un test para ser utilizado en investigaciones posteriores por medio de un estudio piloto.Most injuries that occur by performing a formal physical activity are due to a lack of guidance in the implementation of both the activity and the use of the necessary equipment for each activity. While the advice of the implementation is the responsibility of the professionals in charge, the use of the tools can be seen hampered by the ergonomics. Increasingly often, sporting goods manufacturers seek to include mobile and adjustable parts on their machines to facilitate their adaptation to the characteristics of the larger number of potential users. However, these tend to be invalid settings for the characteristics of the elderly, preventing the practice of the elderly people. This research aims to determine the modulating variables in the perception on ergonomics by the elderly concerning the own physical activity. Considering the structural and functional aspects of the gyms and the elderly, take a sample of subject older than 55 years who received a questionnaire ad hoc in order to know if self-perception differs depending on the age of the participants, the physical activity frequency and the ergonomic quality of resources and facilities. This paper presents the validation of a test to be used in future research through a pilot study.peerReviewe

Redes de emprendimiento: percepción y efectos en la cultura emprendedora

The numerous economic and social changes arising from the current situation of financial crisis, has raised the need to advance research on the processes leading to the promotion of entrepreneurship as a basic competence that allows the acquisition of skills aimed at successful social development, configuring the entrepreneur as a transforming social agent and driver of growth.The theoretical perception about the phenomenon of entrepreneurship is not individualist, emerging within this field the study of social networks as a valuable asset for the entrepreneur, since it allows them to access resources and information and are a source of competitiveness and development.This article is part of the exploratory study phase of the R + D + I project that aims to determine curricular educational policy actions aimed at incorporating the entrepreneurial culture in the formal educational environment. Thus, the specific objective of this phase is to determine the importance given by the older university students to formal and informal entrepreneurship networks. The choice of this population sector is justified by the guidelines that at a European level focus on the elderly as a valuable resource for entrepreneurship, due to their training, experience, knowledge and skills necessary to participate in the entrepreneurial competence setting.Los numerosos cambios económicos y sociales derivados de la actual situación de crisis financiera, ha planteado la necesidad de avanzar en las investigaciones sobre los procesos conducentes a la promoción del emprendimiento como competencia básica que permita la adquisición de habilidades dirigidas al desenvolvimiento social exitoso, configurándose el emprendedor como agente social transformador e impulsor del crecimiento.La percepción teórica sobre el fenómeno del emprendimiento no es de corte individualista, emergiendo dentro de este campo el estudio de las redes sociales como activo valioso para el emprendedor, ya que les permite acceder a recursos e información y son fuente de competitividad y desarrollo.El presente artículo se enmarca dentro de la fase de estudio exploratorio del proyecto I+D+i que pretende determinar las acciones en política educativa curricular encaminadas a la incorporación de la cultura emprendedora en el ámbito educativo formal. Así, el objetivo específico de esta fase es determinar la importancia otorgada por los alumnos universitarios mayores a las redes de emprendimiento formales e informales. La elección de este sector poblacional viene justificada por las directrices que a nivel europeo se centran en las personas mayores como recurso valioso para el emprendimiento, debido a su formación, experiencia, conocimientos y aptitudes necesarias para poder participar en la configuración competencial del emprendedor

Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care : a pragmatic, randomised, non-inferiority clinical trial (OB12)

The trial was financed by Ministerio de Sanidad y Consumo Español through their call for independent clinical research, Orden Ministerial SAS/2377, 2010 (EC10-115, EC10-116, EC10-117, EC10-119, EC10-122); CAIBER—Spanish Clinical Research Network, Instituto de Salud Carlos III (ISCIII) (CAI08/010044); and Gerencia Asistencial de Atención Primaria de Madrid. This study is also supported by the Spanish Clinical Research Network (SCReN), funded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, project number PT13/0002/0007, within the National Research Program I+D+I 2013-2016 and co-funded with European Union ERDF funds (European Regional Development Fund). This project received a grant for the translation and publication of this article from the Foundation for Biomedical Research and Innovation in Primary Care (FIIBAP) Call 2017 for grants to promote research programs.Objectives To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency. Design Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain). Participants 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm. Interventions The IM arm received 1 mg VB12 on alternate days in weeks 1–2, 1 mg/week in weeks 3–8 and 1 mg/month in weeks 9–52. The oral arm received 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. Main outcomes Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction. Results The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were −0.7% (133 out of 135 vs 129 out of 130; 95% CI: −3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: −1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were −6.3% (103 out of 112 vs 115 out of 117; 95% CI: −11.9 to −0.1; p=0.025) and −6.8% (103 out of 140 vs 115 out of 143; 95% CI: −16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>−10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route. Conclusions Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Publisher PDFPeer reviewe