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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.


PubMed | Geriatrics Operative Unit, Italian National Research Center on Aging, Center for Neurobiology of Aging, Nutrition and Aging Center and Biochemical Operative Unit
Type: | Journal: Aging clinical and experimental research | Year: 2016

Cognitive decline and dementia represent a key problem for public health as they heavily impair social functioning and independent living. The development of new strategies to support recommendations for patients and their caregivers may represent an outstanding step forward.To describe the study protocol and methods of My Mind Project: the effect of cognitive training for elderly (Grant No. 154/GR-2009-1584108), which investigates, by the use of a multidisciplinary approach, the effects of a comprehensive cognitive training programme on performances in aged subjects with mild-moderate Alzheimers disease, mild cognitive impairment and normal cognitive functioning.The study is a prospective randomized intervention for the assessment of cognitive training effects in three groups of elderly subjects with different cognitive status. A total of 321 elderly people were enrolled in Marche Region, Italy. Each subject was randomly assigned to an experimental group or to a control group. Cognitive performances and biochemical blood markers have also been analysed before cognitive training (baseline), immediately after termination (follow-up 1), after 6months (follow-up 2) and after 2years (follow-up 3).The results will be useful to identify some efficient programmes for the enhancement of cognitive performance in elderly with and without cognitive decline.The application of a non-pharmacological approach in the treatment of elderly with cognitive disorders could have a profound impact on National Health Service.


PubMed | Center for Neurobiology of Aging and Marche Polytechnic University
Type: | Journal: Frontiers in aging neuroscience | Year: 2015

Alzheimers 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.


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.


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.


PubMed | Geriatrics Operative Unit, Center for Neurobiology of Aging and Laboratory of Biostatistics
Type: Journal Article | Journal: Journal of Alzheimer's disease : JAD | 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.


Casoli T.,Center for Neurobiology of Aging | Giuli C.,INRCA IRCCS Hospital | Balietti M.,Center for Neurobiology of Aging | Balietti M.,Cellular Bioenergetics Laboratory | And 5 more authors.
Rejuvenation Research | Year: 2014

To identify biomarkers associated with cognitive stimulation of mild cognitive impairment (MCI) patients, we performed quantitative real-time reverse transcriptase polymerase chain reaction for brain-derived neurotrophic factor (BDNF) mRNA in peripheral lymphocytes of MCI and healthy subjects undergoing a multi-component cognitive training (CT) program. CT determined a significant decrease of BDNF mRNA levels in MCI (fold change=0.31) as compared to healthy subjects (fold change=0.86). It has been reported that in MCI there is an increase of BDNF serum levels, and our findings could indicate a positive effect of CT in restoring pre-disease levels of expression. © Copyright 2014, Mary Ann Liebert, Inc. 2014.


Fattorini G.,Marche Polytechnic University | Fattorini G.,Center for Neurobiology of Aging | Antonucci F.,University of Milan | Antonucci F.,CNR Institute of Neuroscience | And 6 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.


PubMed | University of Verona, University of Pavia and Center for Neurobiology of Aging
Type: Journal Article | Journal: Journal of anatomy | Year: 2016

During ageing, a progressive loss of skeletal muscle mass and a decrease in muscle strength and endurance take place, in the condition termed sarcopenia. The mechanisms of sarcopenia are complex and still unclear; however, it is known that muscle atrophy is associated with a decline in the number and/or efficiency of satellite cells, the main contributors to muscle regeneration. Physical exercise proved beneficial in sarcopenia; however, knowledge of the effect of adapted physical exercise on the myogenic properties of satellite cells in aged muscles is limited. In this study the amount and activation state of satellite cells as well as their proliferation and differentiation potential were assessed insitu by morphology, morphometry and immunocytochemistry at light and transmission electron microscopy on 28-month-old mice submitted to adapted aerobic physical exercise on a treadmill. Sedentary age-matched mice served as controls, and sedentary adult mice were used as a reference for an unperturbed control at an age when the capability of muscle regeneration is still high. The effect of physical exercise in aged muscles was further analysed by comparing the myogenic potential of satellite cells isolated from old running and old sedentary mice using an invitro system that allows observation of the differentiation process under controlled experimental conditions. The results of this exvivo and invitro study demonstrated that adapted physical exercise increases the number and activation of satellite cells as well as their capability to differentiate into structurally and functionally correct myotubes (even though the age-related impairment in myotube formation is not fully reversed): this evidence further supports adapted physical exercise as a powerful, non-pharmacological approach to counteract sarcopenia and the age-related deterioration of satellite cell capabilities even at very advanced age.

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