Non-hyperpolarizing GABA B receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1

γ-Aminobutyric acid is the principal inhibitory neurotransmitter in adults, acting through ionotropic chloride-permeable GABAA receptors (GABAARs), and metabotropic GABABRs coupled to calcium or potassium channels, and cyclic AMP signalling. During early development, γ-aminobutyric acid is the main neurotransmitter and is not hyperpolarizing, as GABAAR activation is depolarizing while GABABRs lack coupling to potassium channels. Despite extensive knowledge on GABAARs as key factors in neuronal development, the role of GABABRs remains unclear. Here we address GABABR function during rat cortical development by in utero knockdown (short interfering RNA) of GABABR in pyramidal-neuron progenitors. GABABR short interfering RNA impairs neuronal migration and axon/dendrite morphological maturation by disrupting cyclic AMP signalling. Furthermore, GABABR activation reduces cyclic AMP-dependent phosphorylation of LKB1, a kinase involved in neuronal polarization, and rescues LKB1 overexpression-induced defects in cortical development. Thus, non-hyperpolarizing activation of GABABRs during development promotes neuronal migration and morphological maturation by cyclic AMP/LKB1 signalling

Epilepsy and hypertension: The possible link for sudden unexpected death in epilepsy?

Epilepsy affects about 50 million people worldwide. Sudden unexpected death in epilepsy (SUDEP) is the main cause of death in epilepsy accounting for up to 17% of all deaths in epileptic patients, and therefore remains a major public health problem. SUDEP likely arises from a combination and interaction of multiple risk factors (such as being male, drug resistance, frequent generalized tonic-clonic seizures) making risk prediction and mitigation challenging. While there is a general understanding of the physiopathology of SUDEP, mechanistic hypotheses linking risk factors with a risk of SUDEP are still lacking. Identifying cross-talk between biological systems implicated in SUDEP may facilitate the development of improved models for SUDEP risk assessment, treatment and clinical management. In this review, the aim was to explore an overlap between the pathophysiology of hypertension, cardiovascular disease and epilepsy, and discuss its implication for SUDEP. Presented herein, evidence in literature in support of a cross-talk between the renin–angiotensin system (RAS) and sympathetic nervous system, both known to be involved in the development of hypertension and cardiovascular disease, and as one of the underlying mechanisms of SUDEP. This article also provides a brief description of local RAS in brain neuroinflammation and the role of centrally acting RAS inhibitors in epileptic seizure alleviation

A cell surface biotinylation assay to reveal membrane associated neuronal cues: Negr1 regulates dendritic arborization

A complex and still not comprehensively resolved panel of transmembrane proteins regulates the outgrowth and the subsequent morphological and functional development of neuronal processes. In order to gain a more detailed description of these events at the molecular level, we have developed a cell surface biotinylation assay to isolate, detect, and quantify neuronal membrane proteins. When we applied our assay to investigate neuron maturation in vitro, we identified 439 differentially expressed proteins, including 20 members of the immunoglobulin superfamily. Among these candidates, we focused on Negr1, a poorly described cell adhesion molecule. We demonstrated that Negr1 controls the development of neurite arborization in vitro and in vivo. Given the tight correlation existing among synaptic cell adhesion molecules, neuron maturation, and a number of neurological disorders, our assay results are a useful tool that can be used to support the understanding of the molecular bases of physiological and pathological brain function

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

Intracellular chloride ([Cl-](i)) andpH(pH(i)) are fundamental regulators of neuronal excitability. They exert wide-ranging effects on synaptic signaling and plasticity and on development and disorders of the brain. The ideal technique to elucidate the underlying ionic mechanisms is quantitative and combined two-photon imaging of [Cl-](i) and pH(i), but this has never been performed at the cellular level in vivo. Here, by using a genetically encoded fluorescent sensor that includes a spectroscopic reference (an element insensitive to Cl-and pH), we show that ratiometric imaging is strongly affected by the optical properties of the brain. We have designed a method that fully corrects for this source of error. Parallel measurements of [Cl-](i) and pH(i) at the single-cell level in the mouse cortex showed the in vivo presence of the widely discussed developmental fall in [Cl-](i) and the role of the K-Cl cotransporter KCC2 in this process. Then, we introduce a dynamic two-photon excitation protocol to simultaneously determine the changes of pHi and [Cl-](i) in response to hypercapnia and seizure activity.Peer reviewe

Multiculturalism in education in Spain

The article addresses the multifaceted issues of cultural diversity in contemporary Spain. Multiculturalism is perceived from the perspective of ethnic minorities and immigrant students in, mainly, compulsory schooling. Legal framework for the school system is followed by the description of inequalities in education. The aspect of segregation or even marginalization of immigrant alumni and their significantly lower achievement (after PISA reports), when compared to native peers, is strongly emphasized. A section dedicated to linguistic pluralism in the Autonomous Communities of Catalonia, the Basque Country and Galicia, gives the way to the country's legal background, as regards cultural diversity. There are also considered the aspects of support through compensatory programmes in the classroom in the light of the policy of normalization

Evaluation of adult education staff – evaluator’s profile

The paper presents the outcomes of the studies on evaluation of adult education staff as a result of training courses for the purpose of the international research project EduEval launched by the European Commission. A brief description of the course aims and activities is followed by its detailed contents, such as: external evaluation, self-assessment and context evaluation. Particular emphasis is put on the profile of adult education staff evaluators by selected markers, among which education and knowledge , skills and competences are of predominant importance. An innovative nature of the EduEval model in terms of quality and usefulness in Polish circumstances regarding the evaluation of adult education staff is strongly stressed, as well.Artykuł przedstawia wyniki badań nad ewaluacją kadry kształcenia dorosłych uzyskane w toku warsztatów szkoleniowych na użytek międzynarodowego projektu badawczego EduEval realizowanego przez Komisję Europejską. Zwięzłemu opisowi celów szkolenia i rodzajów działań towarzyszą treści szczegółowe, a wśród nich: ewaluacja zewnętrzna, samoocena, ewaluacja kontekstowa. Szczególny nacisk położony jest na profil ewaluatora kadry kształcenia dorosłych według wybranych wyznaczników, wśród których dominujące znaczenie mają: wykształcenie i wiedza, umiejętności i kompetencje. Podkreśla się również dobitnie innowacyjny charakter modelu EduEval w zakresie ewaluacji kadry kształcenia dorosłych pod względem jego wartości i użyteczności w warunkach polskich

Preparation, Characterization, and Activation of Natural Glassy Carbon Paste Electrodes as New Sensors for Determining the Total Antioxidant Capacity of Plant Extracts

The continuous search for new sensing materials with high recognition capabilities is necessary to improve existing analytical procedures and to develop new ones. Natural glassy carbon and polydimethylsiloxane were shown to be used for the preparation of carbon paste electrodes to employ them in new, voltammetric, green-chemistry-friendly electroanalytical procedures aimed at evaluating the antioxidant capacity of plant extracts, dietary supplements, and hydrolats. The developed electrodes provided well-shaped and reproducible voltammetric signals (RSD = 1%) of the oxidation of epigallocatechin gallate, the main component of many plants and plant-based formulations with antioxidative activity, in the 1–12.5 µM range (DPV mode, LOD = 0.08 µM). If needed, the performance of new carbon paste electrodes can be further enhanced by the introduction of trivalent rare earth oxides to carbon paste to increase its active surface, facilitate electron transfer, and improve the resolution of recorded signals