Transcriptional diversity in specific synaptic gene sets discriminates cortical neuronal identity.

Synapse diversity has been described from different perspectives, ranging from the specific neurotransmitters released, to their diverse biophysical properties and proteome profiles. However, synapse diversity at the transcriptional level has not been systematically identified across all synapse populations in the brain. To quantify and identify specific synaptic features of neuronal cell types we combined the SynGO (Synaptic Gene Ontology) database with single-cell RNA sequencing data of the mouse neocortex. We show that cell types can be discriminated by synaptic genes alone with the same power as all genes. The cell type discriminatory power is not equally distributed across synaptic genes as we could identify functional categories and synaptic compartments with greater cell type specific expression. Synaptic genes, and specific SynGO categories, belonged to three different types of gene modules: gradient expression over all cell types, gradient expression in selected cell types and cell class- or type-specific profiles. This data provides a deeper understanding of synapse diversity in the neocortex and identifies potential markers to selectively identify synapses from specific neuronal populations.

A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss.

Skeletal muscle regeneration by muscle satellite cells is a physiological mechanism activated upon muscle damage and regulated by Notch signaling. In a family with autosomal recessive limb-girdle muscular dystrophy, we identified a missense mutation in POGLUT1 (protein O-glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and in vivo experiments demonstrated that the mutation reduces O-glucosyltransferase activity on Notch and impairs muscle development. Muscles from patients revealed decreased Notch signaling, dramatic reduction in satellite cell pool and a muscle-specific α-dystroglycan hypoglycosylation not present in patients' fibroblasts. Primary myoblasts from patients showed slow proliferation, facilitated differentiation, and a decreased pool of quiescent PAX7+ cells. A robust rescue of the myogenesis was demonstrated by increasing Notch signaling. None of these alterations were found in muscles from secondary dystroglycanopathy patients. These data suggest that a key pathomechanism for this novel form of muscular dystrophy is Notch-dependent loss of satellite cells.

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones.

KEY POINTS: Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin-phospholipid interaction. ABSTRACT: Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB.

Aplicación retrospectiva del score para meningoencefalitis bacteriana en pacientes ingresados con síndrome neurológico infeccioso durante 5 años: Hospital Provincial Pediátrico Docente Matanzas 2001, 2003-2006 / Retrospective application of the score for bacterial meningoencephalitis in patients admitted with infectious neurological syndrome during 5 years: provincial Teaching Pediatric Hospital Mat:azas 2001, 2003-2006

Introducción: En la práctica clínica pediátrica no siempre resulta fácil la diferenciación entre las meningoencefalitis bacterianas y asépticas, lo cual genera encarecimiento del tratamiento en aquellos casos de meningoencefalitis asépticas, incremento del riesgo potencial de complicaciones, así como mayor impacto familiar. Método: Se realizó un estudio retrospectivo de los pacientes ingresados con el diagnóstico de meningoencefalitis en el Hospital Provincial Pediátrico Docente Eliseo Noel Caamaño, de la ciudad de Matanzas, durante un período de 5 años (377 pacientes), a quienes se les aplicó el score para meningoencefalitis bacteriana. Objetivo: Describir el puntaje al ingreso en los pacientes y clasificarlos en bajo o alto riesgo para meningoencefalitis bacteriana, así como compararlos con los diagnósticos al ingreso y egreso. Resultados: El 100 por ciento de los pacientes con meningoencefalitis bacteriana comprobadas bacteriológicamente mostraron puntaje de 2 o mayor (alto riesgo); también identificó 9 pacientes de bajo riesgo (puntaje de 0) para meningoencefalitis bacteriana, los cuales fueron considerados inicialmente como bacterianas y egresados como meningoencefalitis asépticas. Conclusión: El score para meningoencefalitis bacteriana pudiera ser una herramienta útil en la valoración inicial de los pacientes con síndrome neurológico infeccioso(AU)

In the clinical practice it is not always easy the differentiation between bacterial and aseptic meningoencephalitis, causing the raise of the treatment price in cases of aseptic meningoencephalitis, the increase of the potential risk of complications, and also a bigger familiar impact. We made a retrospective study of the patients admitted with the diagnosis of meningoencephalitis in the Infantile Hospital Eliseo Noel Caamaño during a 5-years period (377 patients), applying them the BMS (bacterial meningoencephalitis score). Our objective was describing the score at patients' admittance, and classifying them as presenting high or low risk for bacterial meningoencephalitis, and also comparing the diagnoses at the admittance and discharge. As a result, 100 percent of the patients with bacterial meningoencephalitis bacteriologically tested showed scores of 2 or higher (high risk); there were also identified 9 low risk patients (score 0 for bacterial meningoencephalitis), who were firstly considered as bacterial positive, and discharged as aseptic meningoencephalitis. The bacterial meningoencephalitis score could be a useful tool in the initial evaluation of the patients with the infectious Neurological Syndrome(AU)

Aplicación retrospectiva del score para meningoencefalitis bacteriana en pacientes ingresados con síndrome neurológico infeccioso durante 5 años: Hospital Provincial Pediátrico Docente Matanzas 2001, 2003-2006 / Retrospective application of the score for bacterial meningoencephalitis in patients admitted with infectious neurological syndrome during 5 years: provincial Teaching Pediatric Hospital Mat:azas 2001, 2003-2006

Introducción: En la práctica clínica pediátrica no siempre resulta fácil la diferenciación entre las meningoencefalitis bacterianas y asépticas, lo cual genera encarecimiento del tratamiento en aquellos casos de meningoencefalitis asépticas, incremento del riesgo potencial de complicaciones, así como mayor impacto familiar. Método: Se realizó un estudio retrospectivo de los pacientes ingresados con el diagnóstico de meningoencefalitis en el Hospital Provincial Pediátrico Docente Eliseo Noel Caamaño, de la ciudad de Matanzas, durante un período de 5 años (377 pacientes), a quienes se les aplicó el score para meningoencefalitis bacteriana. Objetivo: Describir el puntaje al ingreso en los pacientes y clasificarlos en bajo o alto riesgo para meningoencefalitis bacteriana, así como compararlos con los diagnósticos al ingreso y egreso. Resultados: El 100 por ciento de los pacientes con meningoencefalitis bacteriana comprobadas bacteriológicamente mostraron puntaje de 2 o mayor (alto riesgo); también identificó 9 pacientes de bajo riesgo (puntaje de 0) para meningoencefalitis bacteriana, los cuales fueron considerados inicialmente como bacterianas y egresados como meningoencefalitis asépticas. Conclusión: El score para meningoencefalitis bacteriana pudiera ser una herramienta útil en la valoración inicial de los pacientes con síndrome neurológico infeccioso

In the clinical practice it is not always easy the differentiation between bacterial and aseptic meningoencephalitis, causing the raise of the treatment price in cases of aseptic meningoencephalitis, the increase of the potential risk of complications, and also a bigger familiar impact. We made a retrospective study of the patients admitted with the diagnosis of meningoencephalitis in the Infantile Hospital Eliseo Noel Caamaño during a 5-years period (377 patients), applying them the BMS (bacterial meningoencephalitis score). Our objective was describing the score at patients' admittance, and classifying them as presenting high or low risk for bacterial meningoencephalitis, and also comparing the diagnoses at the admittance and discharge. As a result, 100 percent of the patients with bacterial meningoencephalitis bacteriologically tested showed scores of 2 or higher (high risk); there were also identified 9 low risk patients (score 0 for bacterial meningoencephalitis), who were firstly considered as bacterial positive, and discharged as aseptic meningoencephalitis. The bacterial meningoencephalitis score could be a useful tool in the initial evaluation of the patients with the infectious Neurological Syndrome

Cysteine string protein-alpha prevents activity-dependent degeneration in GABAergic synapses.

The continuous release of neurotransmitter could be seen to place a persistent burden on presynaptic proteins, one that could compromise nerve terminal function. This supposition and the molecular mechanisms that might protect highly active synapses merit investigation. In hippocampal cultures from knock-out mice lacking the presynaptic cochaperone cysteine string protein-alpha (CSP-alpha), we observe progressive degeneration of highly active synaptotagmin 2 (Syt2)-expressing GABAergic synapses, but surprisingly not of glutamatergic terminals. In CSP-alpha knock-out mice, synaptic degeneration of basket cell terminals occurs in vivo in the presence of normal glutamatergic synapses onto dentate gyrus granule cells. Consistent with this, in hippocampal cultures from these mice, the frequency of miniature IPSCs, caused by spontaneous GABA release, progressively declines, whereas the frequency of miniature excitatory AMPA receptor-mediated currents (mEPSCs), caused by spontaneous release of glutamate, is normal. However, the mEPSC amplitude progressively decreases. Remarkably, long-term block of glutamatergic transmission in cultures lacking CSP-alpha substantially rescues Syt2-expressing GABAergic synapses from neurodegeneration. These findings demonstrate that elevated neural activity increases synapse vulnerability and that CSP-alpha is essential to maintain presynaptic function under a physiologically high-activity regimen.

Síndrome de hipoventilación alveolar central congénito (Maldicion de Ondina) / Congenital central alveolar hypoventilation syndrome (ONDINES CURSE)

Presentamos una paciente con el diagnóstico de Síndrome de Hipoventilación Alveolar Central Congénito, mostramos sus aspectos clínicos más significativos así como una revisión de la literatura al respecto. No tenemos información de presentación de otro caso similar en la literatura médica nacional...(AU)

Síndrome de hipoventilación alveolar central congénito (Maldicion de Ondina) / Congenital central alveolar hypoventilation syndrome (ONDINES CURSE)

Presentamos una paciente con el diagnóstico de Síndrome de Hipoventilación Alveolar Central Congénito, mostramos sus aspectos clínicos más significativos así como una revisión de la literatura al respecto. No tenemos información de presentación de otro caso similar en la literatura médica nacional...