Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome:therapeutic perspectives for 5-HT1A agonists

Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrome is brainstem dysfunction, which results in autonomic disturbances such as breathing deficits, typified by episodes of breathing cessation intercalated with episodes of hyperventilation or irregular breathing. Defects in numerous neurotransmitter systems have been observed in Rett syndrome both in animal models and patients. Here we dedicate special attention to serotonin due to its role in promoting regular breathing, increasing vagal tone, regulating mood, alleviating Parkinsonian-like symptoms and potential for therapeutic translation. A promising new symptomatic strategy currently focuses on regulation of serotonergic function using highly selective serotonin type 1A (5-HT1A) biased agonists. We address this newly emerging therapy for respiratory brainstem dysfunction and challenges for translation with a holistic perspective of Rett syndrome, considering potential mood and motor effects

Educación Intercultural Bilingüe: actualidad y desafíos periodísticos para una educación inclusiva

El presente trabajo pretende ser un análisis crítico sobre la actualidad de la Educación Intercultural Bilingüe (EIB) en Argentina. La EIB es una de las modalidades obligatorias del sistema escolar nacional según la Ley de Educación n° 26206 sancionada en el año 2006 que garantiza el derecho a la educación pública de todos los habitantes de la Argentina. En el capitulo XI, artículo 52 de la misma refiere a la modalidad de Educación Intercultural Bilingüe como “la modalidad del sistema educativo de los niveles de Educación Inicial, Primaria y Secundaria que garantiza el derecho constitucional de los pueblos indígenas a recibir una educación que contribuya a preservar y fortalecer sus pautas culturales, su lengua, su cosmovisión e identidad étnica”. En este sentido, esta ponencia procura recabar y analizar información sobre la temática para dar cuenta del derecho a la educación que se le vulneran a miles de personas que, por no recibir clases en su idioma, quedan excluidos del sistema escolar. A su vez, también remarcar la vinculación de los medios de comunicación en cuanto a la invisibilización de los Pueblos Originarios.Eje temático: EducaciónFacultad de Periodismo y Comunicación Social (FPyCS

Educación Intercultural Bilingüe: actualidad y desafíos periodísticos para una educación inclusiva

El presente trabajo pretende ser un análisis crítico sobre la actualidad de la Educación Intercultural Bilingüe (EIB) en Argentina. La EIB es una de las modalidades obligatorias del sistema escolar nacional según la Ley de Educación n° 26206 sancionada en el año 2006 que garantiza el derecho a la educación pública de todos los habitantes de la Argentina. En el capitulo XI, artículo 52 de la misma refiere a la modalidad de Educación Intercultural Bilingüe como “la modalidad del sistema educativo de los niveles de Educación Inicial, Primaria y Secundaria que garantiza el derecho constitucional de los pueblos indígenas a recibir una educación que contribuya a preservar y fortalecer sus pautas culturales, su lengua, su cosmovisión e identidad étnica”. En este sentido, esta ponencia procura recabar y analizar información sobre la temática para dar cuenta del derecho a la educación que se le vulneran a miles de personas que, por no recibir clases en su idioma, quedan excluidos del sistema escolar. A su vez, también remarcar la vinculación de los medios de comunicación en cuanto a la invisibilización de los Pueblos Originarios.Eje temático: EducaciónFacultad de Periodismo y Comunicación Social (FPyCS

Educación Intercultural Bilingüe: actualidad y desafíos periodísticos para una educación inclusiva

El presente trabajo pretende ser un análisis crítico sobre la actualidad de la Educación Intercultural Bilingüe (EIB) en Argentina. La EIB es una de las modalidades obligatorias del sistema escolar nacional según la Ley de Educación n° 26206 sancionada en el año 2006 que garantiza el derecho a la educación pública de todos los habitantes de la Argentina. En el capitulo XI, artículo 52 de la misma refiere a la modalidad de Educación Intercultural Bilingüe como “la modalidad del sistema educativo de los niveles de Educación Inicial, Primaria y Secundaria que garantiza el derecho constitucional de los pueblos indígenas a recibir una educación que contribuya a preservar y fortalecer sus pautas culturales, su lengua, su cosmovisión e identidad étnica”. En este sentido, esta ponencia procura recabar y analizar información sobre la temática para dar cuenta del derecho a la educación que se le vulneran a miles de personas que, por no recibir clases en su idioma, quedan excluidos del sistema escolar. A su vez, también remarcar la vinculación de los medios de comunicación en cuanto a la invisibilización de los Pueblos Originarios.Eje temático: EducaciónFacultad de Periodismo y Comunicación Social (FPyCS

Prácticas Territoriales en el IUNMa: Una propuesta integral para hacer (y ser) la Universidad que deseamos

Planning and reflecting on the integration of functions from the annual and mandatory curriculum of Territorial Practices, of the degree in Communication of the National University Institute of Human Rights Mothers of the Plaza de Mayo (IUNMa), places us in the exercise of the systematization of our teaching and pedagogical practices, focusing on the importance of students as active subjects in the teaching and learning process but above all, on the need for an open university that rescues its history, revalues ​​and builds from its own identity, from their contexts and social actors of the territory that inhabit it, to form a university by and for the People.Planificar y reflexionar sobre la integración de las funciones desde la currícula anual y obligatoria de Prácticas Territoriales, de la licenciatura en Comunicación del Instituto Universitario Nacional de Derechos Humanos Madres de Plaza de Mayo (IUNMa), nos ubica en el ejercicio de la sistematización de nuestras prácticas docentes y pedagógicas, poniendo el foco en la importancia de los y las estudiantes como sujetos activos del proceso de enseñanza y aprendizaje pero sobre todo, en la necesidad de una universidad abierta que rescate su historia, que revalorice y construya desde su propia identidad, desde sus contextos y actores sociales del territorio que la habitan, para conformar una universidad por y para el Pueblo

Territorial Internships at the IUNMa: A comprehensive proposal to make (and be) the University we want

Planificar y reflexionar sobre la integración de las funciones desde la currícula anual y obligatoria de Prácticas Territoriales, de la licenciatura en Comunicación del Instituto Universitario Nacional de Derechos Humanos Madres de Plaza de Mayo (IUNMa), nos ubica en el ejercicio de la sistematización de nuestras prácticas docentes y pedagógicas, poniendo el foco en la importancia de los y las estudiantes como sujetos activos del proceso de enseñanza y aprendizaje pero sobre todo, en la necesidad de una universidad abierta que rescate su historia, que revalorice y construya desde su propia identidad, desde sus contextos y actores sociales del territorio que la habitan, para conformar una universidad por y para el Pueblo.Planning and reflecting on the integration of functions from the annual and mandatory curriculum of Territorial Practices, of the degree in Communication of the National University Institute of Human Rights Mothers of the Plaza de Mayo (IUNMa), places us in the exercise of the systematization of our teaching and pedagogical practices, focusing on the importance of students as active subjects in the teaching and learning process but above all, on the need for an open university that rescues its history, revalues and builds from its own identity, from their contexts and social actors of the territory that inhabit it, to form a university by and for the People.Dossier: Prácticas universitarias e integralidad: escenarios y problemas actuales en diálogo con la sociedad.Especialización en Docencia Universitari

Temporal profile and mechanisms of the prompt sympathoexcitation following coronary ligation in Wistar rats

Our aim was to assess the timing and mechanisms of the sympathoexcitation that occurs immediately after coronary ligation. We recorded thoracic sympathetic (tSNA) and phrenic activities, heart rate (HR) and perfusion pressure in Wistar rats subjected to either ligation of the left anterior descending coronary artery (LAD) or Sham operated in the working heart-brainstem preparation. Thirty minutes after LAD ligation, tSNA had increased (basal: 2.5±0.2 µV, 30 min: 3.5±0.3 µV), being even higher at 60 min (5.2±0.5 µV, P<0.01); while no change was observed in Sham animals. HR increased significantly 45 min after LAD (P<0.01). Sixty minutes after LAD ligation, there was: (i) an augmented peripheral chemoreflex - greater sympathoexcitatory response (50, 45 and 27% of increase to 25, 50 and 75 µL injections of NaCN 0.03%, respectively, when compared to Sham, P<0.01); (ii) an elevated pressor response (32±1 versus 23±1 mmHg in Sham, P<0.01) and a reduced baroreflex sympathetic gain (1.3±0.1 versus Sham 2.0±0.1%.mmHg-1, P<0.01) to phenylephrine injection; (iii) an elevated cardiac sympathetic tone (ΔHR after atenolol: -108±8 versus -82±7 bpm in Sham, P<0.05). In contrast, no changes were observed in cardiac vagal tone and bradycardic response to both baroreflex and chemoreflex between LAD and Sham groups. The immediate sympathoexcitatory response in LAD rats was dependent on an excitatory spinal sympathetic cardiocardiac reflex, whereas at 3 h an angiotensin II type 1 receptor mechanism was essential since Losartan curbed the response by 34% relative to LAD rats administered saline (P<0.05). A spinal reflex appears key to the immediate sympathoexcitatory response after coronary ligation. Therefore, the sympathoexcitatory response seems to be maintained by an angiotensinergic mechanism and concomitant augmentation of sympathoexcitatory reflexes

A perspective on "cure" for Rett syndrome

The reversal of the Rett syndrome disease process in the Mecp2 mouse model of Guy et al. (2007) has motivated families and researchers to work on this condition. The reversibility in adult mice suggests that there is potentially much to be gained from rational treatments applied to patients of any age. However, it may be difficult to strike the right balance between enthusiasm on the one hand and realism on the other. One effect of this has been a fragmentation of the “Rett syndrome community” with some groups giving priority to work aimed at a cure while fewer resources are devoted to medical or therapy-based interventions to enhance the quality of life of affected patients or provide support for their families. Several possible therapeutic approaches are under development that, it is claimed and hoped, may lead to a “cure” for patients with Rett syndrome. While all have a rationale, there are potential obstacles to each being both safe and effective. Furthermore, any strategy that succeeded in restoring normal levels of MECP2 gene expression throughout the brain carries potential pitfalls, so that it will be of crucial importance to introduce any clinical trials of such therapies with great care. Expectations of families for a radical, rational treatment should not be inflated beyond a cautious optimism. This is particularly because affected patients with us now may not be able to reap the full benefits of a “cure”. Thus, interventions aimed at enhancing the quality of life of affected patients should not be forgone and their importance should not be minimised

Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome

Rett syndrome (RTT) is a severe developmental disorder that is strongly linked to mutations in the MECP2 gene. RTT has been associated with sudden unexplained death and ECG QT interval prolongation. There are mixed reports regarding QT prolongation in mouse models of RTT, with some evidence that loss of Mecp2 function enhances cardiac late Na current, I(Na,Late). The present study was undertaken in order to investigate both ECG and ventricular AP characteristics in the Mecp2(Null/Y) male murine RTT model and to interrogate both fast I(Na) and I(Na,Late) in myocytes from the model. ECG recordings from 8–10-week-old Mecp2(Null/Y) male mice revealed prolongation of the QT and rate corrected QT (QTc) intervals and QRS widening compared to wild-type (WT) controls. Action potentials (APs) from Mecp2(Null/Y) myocytes exhibited longer APD(75) and APD(90) values, increased triangulation and instability. I(Na,Late) was also significantly larger in Mecp2(Null/Y) than WT myocytes and was insensitive to the Nav1.8 inhibitor A-803467. Selective recordings of fast I(Na) revealed a decrease in peak current amplitude without significant voltage shifts in activation or inactivation V(0.5). Fast I(Na) ‘window current’ was reduced in RTT myocytes; small but significant alterations of inactivation and reactivation time-courses were detected. Effects of two I(Na,Late) inhibitors, ranolazine and GS-6615 (eleclazine), were investigated. Treatment with 30 µM ranolazine produced similar levels of inhibition of I(Na,Late) in WT and Mecp2(Null/Y) myocytes, but produced ventricular AP prolongation not abbreviation. In contrast, 10 µM GS-6615 both inhibited I(Na,Late) and shortened ventricular AP duration. The observed changes in I(Na) and I(Na,Late) can account for the corresponding ECG changes in this RTT model. GS-6615 merits further investigation as a potential treatment for QT prolongation in RTT

Deficiency of GABAergic synaptic inhibition in the Kölliker-Fuse area underlies respiratory dysrhythmia in a mouse model of Rett syndrome

Life threatening breathing irregularity and central apnoeas are highly prevalent in children suffering from Rett syndrome. Abnormalities in inhibitory synaptic transmission have been associated with the physiopathology of this syndrome, and may underlie the respiratory disorder. In a mouse model of Rett syndrome, GABAergic terminal projections are markedly reduced in the Kölliker–Fuse nucleus (KF) in the dorsolateral pons, an important centre for control of respiratory rhythm regularity. Administration of a drug that augments endogenous GABA localized to this region of the pons reduced the incidence of apnoea and the respiratory irregularity of Rett female mice. Conversely, the respiratory disorder was recapitulated by blocking GABAergic transmission in the KF area of healthy rats. This study helps us understand the mechanism for generation of respiratory abnormality in Rett syndrome, pinpoints a brain site responsible and provides a clear anatomical target for the development of a translatable drug treatment