Nacher J.,University of Valencia |
Nacher J.,Fundacion Hospital Clinico Universitario Of Valencia |
Nacher J.,Spanish National Network for Research in Mental Health |
Guirado R.,University of Valencia |
And 2 more authors.
Neuronal structural plasticity is known to have a major role in cognitive processes and in the response of the CNS to aversive experiences. This type of plasticity involves processes ranging from neurite outgrowth/retraction or dendritic spine remodeling, to the incorporation of new neurons to the established circuitry. However, the study of how these structural changes take place has been focused mainly on excitatory neurons, while little attention has been paid to interneurons. The exploration of these plastic phenomena in interneurons is very important, not only for our knowledge of CNS physiology, but also for understanding better the etiology of different psychiatric and neurological disorders in which alterations in the structure and connectivity of inhibitory networks have been described. Here we review recent work on the structural remodeling of interneurons in the adult brain, both in basal conditions and after chronic stress or sensory deprivation. We also describe studies from our laboratory and others on the putative mediators of this interneuronal structural plasticity, focusing on the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule is expressed by some interneurons in the adult CNS and, through its anti-adhesive and insulating properties, may participate in the remodeling of their structure. Finally, we review recent findings on the possible implication of PSA-NCAM on the remodeling of inhibitory neurons in certain psychiatric disorders and their treatments. © 2013 Springer Science+Business Media New York. Source
Guirado R.,University of Valencia |
Guirado R.,University of Helsinki |
Perez-Rando M.,University of Valencia |
Sanchez-Matarredona D.,University of Valencia |
And 9 more authors.
Excitatory neurons undergo dendritic spine remodeling in response to different stimuli. However, there is scarce information about this type of plasticity in interneurons. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is a good candidate to mediate this plasticity as it participates in neuronal remodeling and is expressed by some mature cortical interneurons, which have reduced dendritic arborization, spine density, and synaptic input. To study the connectivity of the dendritic spines of interneurons and the influence of PSA-NCAM on their dynamics, we have analyzed these structures in a subpopulation of fluorescent spiny interneurons in the hippocampus of glutamic acid decarboxylase-enhanced green fluorescent protein transgenic mice. Our results show that these spines receive excitatory synapses. The depletion of PSA in vivo using the enzyme Endo-Neuraminidase-N (Endo-N) increases spine density when analyzed 2 days after, but decreases it 7 days after. The dendritic spine turnover was also analyzed in real time using organotypic hippocampal cultures: 24 h after the addition of EndoN, we observed an increase in the apparition rate of spines. These results indicate that dendritic spines are important structures in the control of the synaptic input of hippocampal interneurons and suggest that PSA-NCAM is relevant in the regulation of their morphology and connectivity. © The Author 2013. Source
Forteza M.J.,Hospital Clinico Universitario |
Forteza M.J.,University of Valencia |
Forteza M.J.,Fundacion Hospital Clinico Universitario Of Valencia |
Novella S.,University of Valencia |
And 18 more authors.
European Journal of Clinical Investigation
Background: In patients with ST-segment elevation myocardial infarction (STEMI) reperfused with primary coronary intervention (PCI), the dynamics of endothelial cell (EC) viability, apoptosis and necrosis and its relationship with the structural consequences on the left ventricle have not been addressed so far. Design: In 20 STEMI patients, we incubated human umbilical vein endothelial cells (HUVECs) with serum drawn before reperfusion and subsequently afterwards (24, 96 h, 30 days). Viability, apoptosis and necrosis percentages were evaluated by flow cytometry. Values were compared with 12 age- and sex-matched control subjects with normal coronary arteries. Cardiac magnetic resonance (CMR) was performed during the first week after infarction. Results: Serum from STEMI patients induced a progressive loss of EC viability, with a nadir of 67·7 ± 10·2% at 96 h (baseline: 75 ± 6% and controls: 80·2 ± 3·9%, P < 0·001 in both cases). This is due to an increase in apoptosis that peaked at 96 h after reperfusion (15·2 ± 7·1% vs. 11 ± 6 at baseline and 5·8 ± 1·6% in controls, P < 0·001 in both cases). However, no significant dynamic changes in EC necrosis were detected. Extensive myocardial oedema (> 30%, median of left ventricular mass) was the only CMR variable significantly associated with a higher percentage of EC apoptosis at 96 h (extensive vs. nonextensive oedema: 18·3 ± 6·8% vs. 12·1 ± 6·3%, P < 0·05). Conclusions: Dynamic changes in EC viability occur in the setting of STEMI patients reperfused with PCI, these changes peak late after reperfusion, they are mainly the result of an increase of apoptosis and are associated with the presence of extensive myocardial oedema. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Source