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Le Grazie di Ancona, Italy

Balietti M.,Center for Neurobiology of Aging | Giuli C.,Geriatrics Operative Unit | Fattoretti P.,Center for Neurobiology of Aging | Fabbietti P.,Laboratory of Biostatistics | And 3 more authors.
Journal of Alzheimer's Disease | Year: 2016

We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI-P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE-s): patients with MMSE-s <26 (Subgroup 1) had significantly higher activity than those with MMSE-s ≥26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2A correlates with the cognitive conditions of MCI-P, and that CS acts selectively on subjects with a dysregulated tPLA2A. © 2016 - IOS Press and the authors. All rights reserved.

Casoli T.,Center for Neurobiology of Aging | Di Stefano G.,Center for Neurobiology of Aging | Conti F.,Center for Neurobiology of Aging | Conti F.,Marche Polytechnic University
Frontiers in Aging Neuroscience | Year: 2015

Alzheimer's disease (AD) is the most common form of dementia in the elderly. The vast majority of cases are not linked to a known genetic defect and the molecular mechanisms underlying AD pathogenesis are still elusive. Evidence suggests that mitochondrial dysfunction is a prominent feature of the disease, and that mitochondrial DNA (mtDNA) alterations may represent a possible starting point of the pathophysiological cascade. Although specific mtDNA alterations have been reported in AD patients both in brain and peripheral tissues, such as D-loop mutations, 4977-bp deletion and poly-C tract D310 cytosine insertion, a generalized subtle allelic shift has also been demonstrated. This shift is significant for a few nucleotide positions (nps), but it is also detectable for most nps, although at a lower level. As single allelic substitutions can unlikely be determinant, it is proposed that the combination of all of them could lead to a less efficient oxidative phosphorylation, thus influencing AD development and course. © 2015 Casoli, Spazzafumo, Di Stefano and Conti.

Fattorini G.,Marche Polytechnic University | Fattorini G.,Center for Neurobiology of Aging | Antonucci F.,University of Milan | Antonucci F.,CNR Institute of Neuroscience | And 4 more authors.
Journal of Cell Science | Year: 2015

In adult neocortex, VGLUT1 (also known as SLC17A7), the main glutamate vesicular transporter, and VGAT (also known as SLC32A1), the c-aminobutyric acid (GABA) vesicular transporter, are co-expressed in a subset of axon terminals forming both symmetric and asymmetric synapses, where they are sorted into the same vesicles. However, the functional consequence of this colocalization in cortical neurons has not been clarified. Here, we tested the hypothesis that cortical axon terminals co-expressing VGLUT1 and VGAT can evoke simultaneously monosynaptic glutamate and GABA responses, and investigated whether the amount of terminals co-expressing VGLUT1 and VGAT is affected by perturbations of excitation-inhibition balance. In rat primary cortical neurons, we found that a proportion of synaptic and autaptic responses were indeed sensitive to consecutive application of selective glutamate and GABAA receptor blockers. These 'mixed' synapses exhibited paired-pulse depression. Notably, reducing the activity of the neuronal network by treatment with glutamate receptor antagonists decreased the amount of 'mixed' synapses, whereas reducing spontaneous inhibition by treatment with bicuculline increased them. These synapses might contribute to homeostatic regulation of excitation-inhibition balance. © 2015. Published by The Company of Biologists Ltd.

Cristovao-Ferreira S.,University of Lisbon | Navarro G.,University of Barcelona | Brugarolas M.,University of Barcelona | Perez-Capote K.,University of Barcelona | And 12 more authors.
Purinergic Signalling | Year: 2013

Astrocytes play a key role in modulating synaptic transmission by controlling extracellular gamma-aminobutyric acid (GABA) levels via GAT-1 and GAT-3 GABA transporters (GATs). Using primary cultures of rat astrocytes, we show here that a further level of regulation of GABA uptake occurs via modulation of the GATs by the adenosine A1 (A1R) and A2A (A2AR) receptors. This regulation occurs through A1R-A2AR heteromers that signal via two different G proteins, Gs and Gi/0, and either enhances (A2AR) or inhibits (A1R) GABA uptake. These results provide novel mechanistic insight into how GPCR heteromers signal. Furthermore, we uncover a previously unknown mechanism where adenosine, in a concentration-dependent manner, acts via a heterocomplex of adenosine receptors in astrocytes to significantly contribute to neurotransmission at the tripartite (neuron-glia-neuron) synapse. © 2013 Springer Science+Business Media Dordrecht.

Melone M.,Marche Polytechnic University | Melone M.,Center for Neurobiology of Aging | Ciappelloni S.,Marche Polytechnic University | Conti F.,Marche Polytechnic University | And 2 more authors.
Frontiers in Neuroanatomy | Year: 2014

Cortical GABAergic synapses exhibit a high degree of molecular, anatomical and functional heterogeneity of their neurons of origins, presynaptic mechanisms, receptors, and scaffolding proteins. GABA transporters (GATs) have an important role in regulating GABA levels; among them, GAT-1 and GAT-3 play a prominent role in modulating tonic and phasic GABAAR-mediated inhibition. We asked whether GAT-1 and GAT-3 contribute to generating heterogeneity by studying their ultrastructural localization at cortical symmetric synapses using pre-and post-embedding electron microcopy. GAT-1 and GAT-3 staining at symmetric synapses showed that in some cases the transporters were localized exclusively over axon terminals; in others they were in both axon terminals and perisynaptic astrocytic processes; and in some others GAT-1 and GAT-3 were in perisynaptic astrocytic processes only. Moreover, we showed that the organizational pattern of GAT-1, but not of GAT-3, exhibits a certain degree of specificity related to the post-synaptic target of GABAergic synapses. These findings show that symmetric synapses expressing GAT-1 or GAT-3 are heterogeneous, and indicate that plasma membrane transporters can contribute to synaptic heterogeneity. © 2014 Melone, Ciappelloni and Conti.

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