Center for Neurobiology of Aging
Center for Neurobiology of Aging
Bragina L.,Marche Polytechnic University |
Bragina L.,Center for Neurobiology of Aging |
Fattorini G.,Marche Polytechnic University |
Fattorini G.,Center for Neurobiology of Aging |
And 6 more authors.
Frontiers in Cellular Neuroscience | Year: 2013
Analysis of presynaptic protein expression in glutamatergic and GABAergic central synapses performed in several laboratories and with different techniques is unveiling a complex scenario, largely because each presynaptic protein exists in several isoforms. The interpretation of these findings is generally based on the notion that each synapse and each synaptic vesicle contains one of the isoforms of each family of presynaptic proteins. We verified whether this interpretation is tenable by performing triple labeling and immunoisolation studies with the aim of detecting two isoforms of a given presynaptic protein in glutamatergic or GABAergic axon terminals and/or synaptic vesicles. Here, we show that: 1) the possibility that not all families of presynaptic proteins are expressed in all terminals must be taken into serious account; 2) the expression of a given protein isoform in a terminal does not exclude the expression of other isoforms of the same protein in the same terminal and in the same vesicle. These conclusions open new and interesting problems; their experimental analysis might improve our understanding of the physiology and pathophysiology of central synapses. © 2013 Bragina, Fattorini, Giovedì, Bosco, Benfenati and Conti.
Milanese M.,University of Genoa |
Giribaldi F.,University of Genoa |
Melone M.,Marche Polytechnic University |
Melone M.,Instituto Giannina Gaslini |
And 13 more authors.
Neurobiology of Disease | Year: 2014
Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease reflecting degeneration of upper and lower motoneurons (MNs). The cause of ALS and the mechanisms of neuronal death are still largely obscure, thus impairing the establishment of efficacious therapies. Glutamate (Glu)-mediated excitotoxicity plays a major role in MN degeneration in ALS. We recently demonstrated that the activation of Group I metabotropic Glu autoreceptors, belonging to both type 1 and type 5 receptors (mGluR1 and mGluR5), at glutamatergic spinal cord nerve terminals, produces excessive Glu release in mice over-expressing human superoxide-dismutase carrying the G93A point mutation (SOD1G93A), a widely used animal model of human ALS. To establish whether these receptors are implicated in ALS, we generated mice expressing half dosage of mGluR1 in the SOD1G93A background (SOD1G93AGrm1crv4/+), by crossing the SOD1G93A mutant mouse with the Grm1crv4/+ mouse, lacking mGluR1 because of a spontaneous recessive mutation. SOD1G93AGrm1crv4/+ mice showed prolonged survival probability, delayed pathology onset, slower disease progression and improved motor performances compared to SOD1G93A mice. These effects were associated to reduction of mGluR5 expression, enhanced number of MNs, decreased astrocyte and microglia activation, normalization of metallothionein and catalase mRNA expression, reduced mitochondrial damage, and decrease of abnormal Glu release in spinal cord of SOD1G93AGrm1crv4/+compared to SOD1G93A mice. These results demonstrate that a lower constitutive level of mGluR1 has a significant positive impact on mice with experimental ALS, thus providing the rationale for future pharmacological approaches to ALS by selectively blocking Group I metabotropic Glu receptors. © 2013 The Authors.
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.
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.
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.