Autoimmune inflammation triggers aberrant astrocytic calcium signaling to impair synaptic plasticity.

Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in multiple sclerosis initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we unveil deregulation of astrocytic calcium signaling and astrocyte-to-neuron communication as key pathophysiological mechanisms of cortical dysfunction in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Using two-photon imaging ex vivo and fiber photometry in freely behaving mice, we found that acute EAE was associated with the emergence of spontaneously hyperactive cortical astrocytes exhibiting dysfunctional responses to cannabinoid, glutamate and purinoreceptor agonists. Abnormal astrocyte signaling by Gi and Gq protein coupled receptors was observed in the inflamed cortex. This was mirrored by treatments with pro-inflammatory factors both in vitro and ex vivo, suggesting cell-autonomous effects of the cortical neuroinflammatory environment. Finally, deregulated astrocyte calcium activity was associated with an enhancement of glutamatergic gliotransmission and a shift of astrocyte-mediated short-term and long-term plasticity mechanisms towards synaptic potentiation. Overall, our data identify astrocyte-neuronal network dysfunctions as key pathological features of gray matter inflammation in multiple sclerosis and potentially additional neuroimmunological disorders.

Nuevas vías de información en el sistema nervioso: comunicación entre astrocitos y neuronas / New information pathways in the nervous system: communication between astrocytes and neurones

Introducción y desarrollo. Los astrocitos, un tipo de célula glial del sistema nervioso central (SNC), se han considerado clásicamente como células de soporte trófico, estructural y metabólico de las neuronas. Sin embargo, en los últimos años numerosas evidencias sugieren un papel más activo de los astrocitos en la fisiología neuronal, y es posible que estén involucrados en el procesamiento de información del SNC. Los astrocitos poseen una forma de excitabilidad basada en variaciones de la concentración intracelular de Ca2+ y se comunican entre ellos mediante ondas de Ca2+ intercelulares. Además, neurotransmisores liberados sinápticamente son capaces de movilizar Ca2+ de los reservorios intracelulares de los astrocitos; es decir, la excitabilidad celular astrocitaria se desencadena por la actividad sináptica neuronal. Por último, los astrocitos pueden liberar el transmisor glutamato de manera dependiente de Ca2+al medio extracelular, y modulan así la actividad eléctrica neuronal y la transmisión sináptica. Como consecuencia de estas nuevas vías de comunicación celular entre astrocitos y neuronas, se ha propuesto el concepto de sinapsis tripartita, que representa una nueva visión de la fisiología sináptica, según la cual la sinapsis está constituida funcionalmente por tres elementos: los elementos presinápticos y posinápticos y los astrocitos adyacentes. Conclusión. Los novedosos resultados que se discuten en la presente revisión demuestran la presencia de nuevas y complejas vías de información en el SNC, basadas en la existencia de comunicación bidireccional entre los astrocitos y las neuronas, con relevantes consecuencias en los mecanismos celulares responsables del procesamiento de información por el SNC (AU)

Introduction and method. Astrocytes, a type of glial cell in the central nervous system (CNS), have been classically considered as trophic, structural and supportive cells for neurons. However, in recent years, accumulating evidence suggest a more active role of astrocytes in the physiology of neurons, being involved in the information processing of the CNS. Astrocytes exhibit both a form of excitability based on variations of the intracellular Ca2+ concentration, and a form of communication based on intercellular Ca2+ waves. Furthermore, synaptically released neurotransmitters mobilize Ca2+ from the astrocytic intracellular stores, i.e., the astrocytic cellular excitability can be triggered by the synaptic activity. Finally, astrocytes release the transmitter glutamate to the extracellular space through a Ca2+-dependent mechanism, modulating the neuronal electrical activity and the synaptic transmission. As a consequence of the demonstration of these new forms of cellular communication between astrocytes and neurons, the concept of ‘tripartite synapse’ has been proposed, in which the synapse is functionally constituted by three elements, i.e., the pre- and postsynaptic elements and the surrounding astrocytes. Conclusion. The novel results discussed in the present review support the presence of new and complex information pathways in the CNS, which are based on the existence of bidirectional communication between astrocytes and neurons, and which have relevant consequences on the cellular mechanisms responsible for the information processing of the CNS (AU)

Distribución de los genotipos del virus C en la población de hemodiálisis de la provincia de Alicante / Hepatitis c virus genotype distribution in the hemodialysis population from Alicante

Los genotipos del virus de la hepatitis C (VHC) se distribuyen irregularmente según las áreas geográficas y los diferentes grupos de riesgo. Objetivo: Conocer la prevalencia y distribución de los genotipos y subtipos del VHC en los pacientes de hemodiálisis (HD) de la provincia de Alicante, analizando la distribución por áreas y su asociación con algunas características como la edad y el tiempo en hemodiálisis. Métodos: Se estudiaron 640 pacientes en HD y se determinó el RNA-VHC y sus genotipos en los 120 pacientes con anticuerpos frente al VHC (Ac-VHC) positivos. Se comparó con un grupo control de 1.355 pacientes de otros grupos de riesgo de la misma área geográfica. Resultados: La prevalencia del VHC en HD fue del 20%. En el 15% (18/120)de los pacientes en HD con Ac-VHC no se detectó el RNA-VHC en suero. Los genotipos de los 102 pacientes con RNA viral positivo (85%) mostraron las siguientes prevalencias: 1b: 56,8% (58/102), 1a: 19,6% (20/102), 3: 17% (17/102),2a-2c: 1,9% (2/102), 2b: 0,9% (1/102), 4: 2,9% (3/102), 5: 0,9% (1/102).Conclusiones: Los genotipos más frecuentes en hemodiálisis en la provincia de (..) (AU)

Hepatitis C virus (HCV) genotypes are irregularly distributed among the different geographic area and groups at risk. Objective: To study the different HCV genotypes and subtypes of hemodialyzed patients from Alicante. Methods: We studied 640 patients on haemodialysis (HD) and we determined the RNA-HCV and the genotypes in the 120 patients with antibodies against HCV(HCV-Ab). We compared the results with the genotypes of 1,370 patients from other groups at risk in the same geographic area. Results: RNA-HCV was not found in the serum in 15% (18/120) of the patients on HD who were HCV-Ab positive. Prevalence of the different genotypes in the102 patients with positive viral RNA was the following: 1b: 56.8% (58/102), 1a:19.6% (20/102), 3: 17% (17/102), 2a-2c: 1.9 (2/102), 2b: 0.9% (1/102) 4: 2.9(3/102), 5: 0.9% (1/102). In conclusion, the genotype 1b was the most frequent in the patients studied in all these areas, and was the same as in the rest of the country. This genotype has been associated with the most severe hepatic disease and poor response to treatment, affecting the prognosis of these patients. The most frequent genotypes in HD in Alicante were 1b, 3 and 1a. HCV genotypes (AU)