Mesenchymal stem cells enhance GABAergic transmission in co-cultured hippocampal neurons

Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent stem cells endowed with neurotrophic potential combined with immunological properties, making them a promising therapeutic tool for neurodegenerative disorders. However, the mechanisms through which MSCs promote the neurological recovery following injury or inflammation are still largely unknown, although cell replacement and paracrine mechanisms have been hypothesized. In order to find out what are the mechanisms of the trophic action of MSCs, as compared to glial cells, on CNS neurons, we set up a co-culture system where rat MSCs (or cortical astrocytes) were used as a feeding layer for hippocampal neurons without any direct contact between the two cell types. The analysis of hippocampal synaptogenesis, synaptic vesicle recycling and electrical activity show that MSCs were capable to support morphological and functional neuronal differentiation. The proliferation of hippocampal glial cells induced by the release of bioactive substance(s) from MSCs was necessary for neuronal survival. Furthermore, MSCs selectively increased hippocampal GABAergic pre-synapses. This effect was paralleled with a higher expression of the potassium/chloride KCC2 co-transporter and increased frequency and amplitude of mIPSCs and sIPSCs. The enhancement of GABA synapses was impaired by the treatment with K252a, a Trk/neurotrophin receptor blocker, and by TrkB receptor bodies hence suggesting the involvement of BDNF as a mediator of such effects. The results obtained here indicate that MSC-secreted factors induce glial-dependent neuronal survival and trigger an augmented GABAergic transmission in hippocampal cultures, highlighting a new effect by which MSCs could promote CNS repair. Our results suggest that MSCs may be useful in those neurological disorders characterized by an impairment of excitation versus inhibition balance

Ascending aorta phenotypic and genotypic changes in bicuspid aortic valve disease

Bicuspid aortic valve (BAV) with left-right (L-R), right-non coronary (R-NC) and left-non coronary (L-NC) cusp fusion represents distinct pathological entities and the rate of aortic enlargement varies according to the pattern of cusps fusion (1). Here, we investigated the histological features of aneurysms associated to different BAV phenotypes and we looked for specific microRNAs (miRNA) as biomarkers of medial degeneration severity. Aortic specimens and blood were obtained from BAV patients treated surgically for the repair of thoracic aortic aneurysm and were divided into two groups: low grade medial degeneration (LGMD, n=10); high grade medial degeneration (HGMD, n=10). A control group (CN, n=10), with tricuspid aortic valve not associated to aortopathy, was also involved in the study. We performed commonly used morphological staining to evaluate medionecrosis, fibrosis, elastic fragmentation and mucoid material accumulation. We detected MMP9 and MMP2 immunoreactivity and tunel assay. Moreover, we measured the expression patterns of miR-122, miR-130, miR-718, miR-486 by RT-qPCR. MMP2 and MMP9 expression increased in HGMD compared to LGMD and control group. Apoptotic cells were observed in the sub intimal region of the media in HGMD group. The expression levels of miR-718 and miR-122 in aortic specimens significantly decreased in LGMD and HGMD groups compared to CN and negatively correlated with the ascending aorta wall score. Moreover, the expression levels of miR-130 significantly decreased in LGMD group compared to CN. HGMD group showed a significant increase of miR-486 expression levels compared to CN and LGMD. Plasma expression levels of miR-718 significantly decreased in LGMD compared to CN. Interestingly, miR-486 expression levels significantly increased in HGMD group compared to the CN and positively correlated with the ascending aorta wall score. Our work suggests miR-718 and miR-486 might be considered as new non-invasive biomarkers of aorta wall degeneration in BAV due their association with the morphological features of the vessel. A significant dysregulation of these biomarkers might be associated with high risk of dissection and rupture

L'editoria napoletana e le trasformazioni del secolo XIX. Esperienze a confronto: Migliaccio, Raimondi, De Simone

De Simone, Raimondi, Migliaccio, tre stampatori che riuscirono a sopravvivere alle profondi mutamenti e alle innumerevoli fratture tra ottocento e novecento. Si analizzano le dinamiche, spesso differenti, che permisero loro di sopravvivere ai mutamenti del temp

Istituzioni e traffici nel Mediterraneo tra età antica e crescita moderna

International audienceLe volume, articulé autour de 4 thèmes, traite du rôle et du poids des institutions par rapport à l’évolution de la navigation et aux problèmes qu’elle rencontre dans certains pays de la Méditerranée. Il se concentre sur les règles en usage, les politiques économiques, consulaires, commerciales, sanitaires, douanières et fiscales, et les contrats de commerce et ’assurance passés dans les zones de frontières internes et externes