227 results on '"Virgili, M."'
Search Results
52. Akt pathway mediates a cGMP-dependent survival role of nitric oxide in cerebellar granule neurones.
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Ciani, E., Virgili, M., and Contestabile, A.
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CELLULAR signal transduction , *APOPTOSIS , *NITRIC oxide - Abstract
Apoptotic death results from disrupting the balance between anti-apoptotic and pro-apoptotic cellular signals. The inter- and intracellular messenger nitric oxide is known to mediate either death or survival of neurones. In the present work, cerebellar granule cells were used as a model to assess the survival role of nitric oxide and to find novel signal transduction pathways related to this role. It is reported that sustained inhibition of nitric oxide production induces apoptosis in differentiated cerebellar granule neurones and that compounds that slowly release nitric oxide significantly revert this effect. Neuronal death was also reverted by a caspase-3-like inhibitor and by a cyclic GMP analogue, thus suggesting that nitric oxide-induced activation of guanylate cyclase is essential for the survival of these neurones. We also report that the Akt/GSK-3 kinase system is a transduction pathway related to the survival action of nitric oxide, as apoptosis caused by nitric oxide deprivation is accompanied by down-regulation of this, but not of other, kinase systems. Conversely, treatments able to rescue neurones from apoptosis also counteracted this down-regulation. Furthermore, in transfection experiments, overexpression of the Akt gene significantly decreased nitric oxide deprivation-related apoptosis. These results are the first evidence for a mechanism where endogenous nitric oxide promotes neuronal survival via Akt/GSK-3 pathway. [ABSTRACT FROM AUTHOR]
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- 2002
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53. Regional- and Age-Specific Neurochemical Alterations in Rats Rendered Microencephalic by Differentially Timed Gestational Methylazoxymethanol Treatment.
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Virgili, M., Barnabei, O., and Contestabile, A.
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- 1989
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54. Kainic Acid Differentially Affects the Synaptosomal Release of Endogenous and Exogenous Amino Acidic Neurotransmitters.
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Poli, A., Contestabile, A., Migani, P., Rossi, L., Rondelli, C., Virgili, M., Bissoli, R., and Barnabei, O.
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- 1985
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55. Topography of neurochemical alterations in the CNS of aged rats
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Virgili, M., Monti, B., Polazzi, E., Angiolini, G., and Contestabile, A.
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- 2001
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56. Regional distribution of nitric oxide synthase and NADPH-diaphorase activities in the central nervous system of teleosts
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Virgili, M., Poli, A., Beraudi, A., Giuliani, A., and Villani, L.
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- 2001
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57. Increase of the ornithine decarboxylase/polyamine system and transglutaminase upregulation in the spinal cord of aged rats
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Virgili, M., Necchi, D., Scherini, E., and Contestabile, A.
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- 2001
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58. Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats
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Virgili, M. and Contestabile, A.
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- 2000
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59. Developmental effects of in vivo and in vitro inhibition of nitric oxide synthase in neurons
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Virgili, M., Monti, B., LoRusso, A., Bentivogli, M., and Contestabile, A.
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- 1999
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60. Simulated ischaemia-reperfusion conditions increase xanthine dehydrogenase and oxidase activities in rat brain slices
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Battelli, M. G., Buonamici, L., Virgili, M., Abbondanza, A., and Contestabile, A.
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- 1998
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61. Effects of chronic lithium treatment on ornithine decarboxylase induction and excitotoxic neuropathology in the rat
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Sparapani, M., Virgili, M., Ortali, F., and Contestabile, A.
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- 1997
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62. Neuronal nitric oxide synthase is permanently decreased in the cerebellum of rats subjected to chronic neonatal blockade of N-methyl-d-aspartate receptors
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Virgili, M., Facchinetti, F., Sparapani, M., Tregnago, M., Lucchi, R., Dall'Olio, R., Gandolfi, O., and Contestabile, A.
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- 1998
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63. Ischemic and excitotoxic damage to brain slices from normal and microencephalic rats
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Virgili, M., Vandi, M., and Contestabile, A.
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- 1997
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64. Absence of excitotoxic neuropathology in microencephalic rats after systemic kainic acid administration
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Virgili, M., Ciani, E., and Contestabile, A.
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- 1996
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65. Alteration of neuronal nitric oxide synthase activity and expression in the cerebellum and the forebrain of microencephalic rats
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Tregnago, M., Virgili, M., Monti, B., Guarnieri, T., and Contestabile, A.
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- 1998
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66. Una deuda histórica
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Aragonés Virgili, M.
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- 1963
67. Depletion of cholinergic habenulo-interpeduncular neurons by selectively timed methylazoxymethanol acetate (MAM) treatment during pregnancy
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Virgili, M., primary, Barnabei, O., additional, and Contestibile, A., additional
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- 1988
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68. Synaptosomal release of newly-synthetized or recently accumulated amino acids. Differential effects of kainic acid on naturally occurring excitatory amino acids and on [d-3H]aspartate
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VIRGILI, M, primary, POLI, A, additional, CONTESTABILE, A, additional, MIGANI, P, additional, and BARNABEI, O, additional
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- 1986
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69. ChemInform Abstract: Chiral (E,E)-1,4-Dialkoxy-1,3-butadienes. Part 1. Stereoselective Synthesis.
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VIRGILI, M., MOYANO, A., PERICAS, M. A., and RIERA, A.
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- 1997
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70. ChemInform Abstract: Bis(tert-butylsulfonyl)acetylene as a General Synthetic Equivalent of Alkynes in Diels-Alder Chemistry. Part 1. Highly Selective Reduction and Alkylating Monodesulfonylation of Z-1,2-Bis(tert-butylsulfonyl) ethenes.
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BELLOCH, J., VIRGILI, M., MOYANO, A., PERICAS, M. A., and RIERA, A.
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- 1992
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71. Quinolinic acid but not MK-801 protects the dopaminergic system from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in goldfish retina
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Guarnieri, T., Virgili, M., Carraro, S., and Villani, L.
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- 1994
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72. Excitotoxic increase of xanthine dehydrogenase and xanthine oxidase in the rat olfactory cortex
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Battelli, M. G., Buonamici, L., Abbondanza, A., and Virgili, M.
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- 1995
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73. Chiral (E,E)-1,4-dialkoxy-1,3-butadienes. 1. Stereoselective synthesis
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VIRGILI, M
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- 1997
74. Every animal matters! Evaluating the selectivity of a Mediterranean bottom trawl fishery from a species community perspective
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Andrea Petetta, Bent Herrmann, Daniel Li Veli, Massimo Virgili, Rocco De Marco, Alessandro Lucchetti, Maravelias, Christos, Petetta A., Herrmann B., Veli D.L., Virgili M., De Marco R., and Lucchetti A.
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Bottom trawling, species and size selectivity, Mediterranean demersal fisheries, discards, catch comparison, fishing performance ,Multidisciplinary - Abstract
Bottom trawl fisheries often catch several species simultaneously. However, most studies addressing the catch performance and selectivity of a specific trawl focus on a few commercially important or most vulnerable species requiring management measures. By contrast, the present study considers the multispecies nature of Mediterranean bottom trawl fisheries through a holistic approach that accounts for the full species community in the catches. Specifically, we evaluated and compared the catch performance of the two codends allowed for this fishery, made of 40 mm square (SM40) and 50 mm diamond (DM50) meshes. Results showed that 50 and 80% of the catch in weight and count numbers, respectively, consisted of species without commercial value, demonstrating that large proportions of the catch are not considered when using the existing approach to evaluate the ecological impact of the fishing activity. Significant differences in catch profiles between the two codends were observed, especially for two commercial flatfish species, Arnoglossus laterna and Citharus linguatula, with larger contributions in the SM40. Further, the SM40 codend had a significantly higher retention, compared to DM50 codend, for specific sizes of Merluccius merluccius and Mullus barbatus. The outcomes of the study can be useful for the Mediterranean bottom trawl fisheries management.
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- 2023
75. Histone Acetylation Defects in Brain Precursor Cells: A Potential Pathogenic Mechanism Causing Proliferation and Differentiation Dysfunctions in Mitochondrial Aspartate-Glutamate Carrier Isoform 1 Deficiency
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Eleonora Poeta, Sabrina Petralla, Giorgia Babini, Brunaldo Renzi, Luigi Celauro, Maria Chiara Magnifico, Simona Nicole Barile, Martina Masotti, Francesca De Chirico, Francesca Massenzio, Luigi Viggiano, Luigi Palmieri, Marco Virgili, Francesco Massimo Lasorsa, Barbara Monti, Poeta E., Petralla S., Babini G., Renzi B., Celauro L., Magnifico M.C., Barile S.N., Masotti M., De Chirico F., Massenzio F., Viggiano L., Palmieri L., Virgili M., Lasorsa F.M., and Monti B.
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white matter disorder ,epigenetics ,oligodendrocytes ,neurons ,Neurosciences. Biological psychiatry. Neuropsychiatry ,SLC25A12/aralar1/AGC1 deficiency ,neuron ,mitochondria ,stomatognathic diseases ,Cellular and Molecular Neuroscience ,nervous system ,epigenetic ,oligodendrocyte ,RC321-571 ,Neuroscience ,Original Research - Abstract
Mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) deficiency is an ultra-rare genetic disease characterized by global hypomyelination and brain atrophy, caused by mutations in the SLC25A12 gene leading to a reduction in AGC1 activity. In both neuronal precursor cells and oligodendrocytes precursor cells (NPCs and OPCs), the AGC1 determines reduced proliferation with an accelerated differentiation of OPCs, both associated with gene expression dysregulation. Epigenetic regulation of gene expression through histone acetylation plays a crucial role in the proliferation/differentiation of both NPCs and OPCs and is modulated by mitochondrial metabolism. In AGC1 deficiency models, both OPCs and NPCs show an altered expression of transcription factors involved in the proliferation/differentiation of brain precursor cells (BPCs) as well as a reduction in histone acetylation with a parallel alteration in the expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, histone acetylation dysfunctions have been dissected in in vitro models of AGC1 deficiency OPCs (Oli-Neu cells) and NPCs (neurospheres), in physiological conditions and following pharmacological treatments. The inhibition of HATs by curcumin arrests the proliferation of OPCs leading to their differentiation, while the inhibition of HDACs by suberanilohydroxamic acid (SAHA) has only a limited effect on proliferation, but it significantly stimulates the differentiation of OPCs. In NPCs, both treatments determine an alteration in the commitment toward glial cells. These data contribute to clarifying the molecular and epigenetic mechanisms regulating the proliferation/differentiation of OPCs and NPCs. This will help to identify potential targets for new therapeutic approaches that are able to increase the OPCs pool and to sustain their differentiation toward oligodendrocytes and to myelination/remyelination processes in AGC1 deficiency, as well as in other white matter neuropathologies.
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- 2022
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76. Effect of Extension Piece Design on Catch Patterns in a Mediterranean Bottom Trawl Fishery
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Andrea Petetta, Bent Herrmann, Massimo Virgili, Daniel Li Veli, Jesse Brinkhof, Alessandro Lucchetti, Petetta, A, Herrmann, B, Virgili, M, Li Veli, D, Brinkhof, J, and Lucchetti, A
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Global and Planetary Change ,Mediterranean demersal fisheries ,T90 turned meshe ,Ocean Engineering ,Aquatic Science ,Oceanography ,Bottom trawling ,Size selectivity ,size selectivity ,T90 turned meshes ,bottom trawling ,trawl extension piece ,Water Science and Technology ,Trawl extension piece - Abstract
The catch composition of bottom trawls is commonly refined and improved through changes in codend design. Measures like reducing the number of meshes in codend circumference or turning diamond netting by 90 degrees are well known to improve the size selectivity of fish species with rounded cross-sectional shape. Based on this we speculated whether the same measures, if applied in other parts of a bottom trawl, would provide similar benefits as in the codend. Therefore, experiments were carried out by deploying these changes to the trawl extension piece in a Mediterranean bottom trawl fishery. However, for European hake and monkfish, results showed no indication of improved selectivity or catch pattern compared to the standard extension piece in the trawl. Contrary, for red mullet, one of the most important species in this fishery, reducing the number of meshes in the circumference of the extension piece jeopardized the size selection obtained in the trawl with a standard extension piece. The lesson learnt from this study was that the design changes that work for the codend do not necessarily work for other parts of the trawl. In fact, they can even have negative effects.
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- 2022
77. Gangliosides attenuate NHDA receptor-mediated excitatory amino acid release in cultured cerebellar neurons
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Nicoletti, F., Cavallaro, B., Bruno, V., Virgili, M., Catania, M.V., Contestabile, A., and Canonico, P.L.
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- 1989
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78. An overview of bottom trawl selectivity in the Mediterranean Sea
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LUCCHETTI, VIRGILI, VASAPOLLO, PETETTA, BARGIONE, LI VELI, BR?IC, SALA, Lucchetti A., Virgili M., Vasapollo C., Petetta A., Bargione G., Veli D.L., Brcic J., and Sala A.
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Mediterranean climate ,Environmental Engineering ,Bottom trawl ,biology ,Trawling ,Fishing ,Sustainable fishery ,Selectivity ,Demersal fish ,Mediterranean Sea ,Aquatic Science ,Oceanography ,Fish stock ,biology.organism_classification ,Bottom trawling ,Fishery ,Mediterranean sea ,Environmental science ,Ecology, Evolution, Behavior and Systematics - Abstract
In the Mediterranean Sea, where bottom trawling for demersal species is the most important fishery in terms of landings, around 75% of the assessed fish stocks are overfished. Its status as one of the world’s most heavily exploited seas and the one subject to the highest trawling pressure has become a global concern. An extensive review of bottom trawl selectivity studies was performed to assess the sustainability of this fishery in the Mediterranean; the selectivity parameters were collected from 93 peer-reviewed publications of 10 countries, totalling 742 records and 65 species. The review highlighted that i) the catch of bottom trawls commonly employed in the Mediterranean, even complying with current regulations on codend meshes, still includes immature individuals for 64-68% of the species investigated, and individuals under the minimum conservation reference size (MCRS) for 78% of the species investigated, and that ii) the MCRS set for 59% of the species analyzed is well below their length at first maturity, and is therefore ecologically inadequate. Although square-mesh codends are slightly more selective, the models developed herein demonstrate that improving size and species selectivity would require considerably larger meshes, which may significantly reduce profitability. The urgent need to reduce the biological impacts of bottom trawling in the Mediterranean should be addressed by promoting the adoption of more ecologically sustainable fishing gears through the introduction of more selective meshes or gear modifications.
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- 2021
79. Pots as alternative and sustainable fishing gears in the Mediterranean Sea: an overview
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Stefano Guicciardi, Alessandro Lucchetti, Andrea Petetta, Massimo Virgili, Petetta A., Virgili M., Guicciardi S., and Lucchetti A.
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biology ,Discard reduction ,Fishing ,Palinurus elephas ,Common octopus ,Pot ,Aquatic Science ,Nephrops ,Sustainable fishery ,biology.organism_classification ,Discards ,Bycatch ,Fishery ,Nephrops norvegicus ,Alternative gear ,Octopus (genus) ,Mediterranean Sea ,Small-scale fishery - Abstract
Stock overexploitation, bycatch, discards and gear impacts on the environment are outstanding issues for Mediterranean fisheries. The adoption of alternative fishing gears is an appealing solution to ensure a more sustainable exploitation of resources. We discuss the pros and cons of pots as alternative gears by reviewing their main designs, spatial distribution and target species in the Mediterranean basin. We assessed the technical factors affecting the catch efficiency of the different pot designs for four target species: spiny lobster, Palinurus elephas; Norway lobster, Nephrops norvegicus; common octopus, Octopus vulgaris and pandalid shrimps, Plesionika spp. We found that pot volume is important to catch Octopus; mesh size to catch Nephrops and Plesionika; entrance surface to catch Octopus, Nephrops and Plesionika; pot shape/colour and entrance shape/position to catch Octopus and Plesionika; and bait type to catch Octopus and Nephrops. The literature review shows that pot fisheries have several considerable advantages over conventional gears, especially in terms of discards, bycatch, seabed impacts (particularly compared with bottom trawls and passive set nets), size and species selectivity, gear depredation, catch quality and gear cost, besides saving time and labour. Disadvantages hampering their wider diffusion include ghost fishing, a low catch of finfish species, the narrow range of species targeted by each pot design and the current early stage of research. These data make a clear case for using pots as alternative gears to traditional ones in the Mediterranean Sea in some areas and seasons to catch certain target species.
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- 2021
80. Age and Growth of Striped Venus Clam Chamelea gallina (Linnaeus, 1758) in the Mid-Western Adriatic Sea: A Comparison of Three Laboratory Techniques
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Massimo Virgili, Giada Bargione, Claudio Vasapollo, Alessandro Lucchetti, Andrea Petetta, Fortunata Donato, Bargione G., Vasapollo C., Donato F., Virgili M., Petetta A., and Lucchetti A.
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acetate peel ,0106 biological sciences ,010504 meteorology & atmospheric sciences ,lcsh:QH1-199.5 ,growth ,Shell (structure) ,Venus ,Ocean Engineering ,Aquatic Science ,lcsh:General. Including nature conservation, geographical distribution ,Von bertalanffy ,Oceanography ,01 natural sciences ,striped venus clam ,Animal science ,Growth rate ,lcsh:Science ,thin sections ,0105 earth and related environmental sciences ,Mathematics ,Water Science and Technology ,Global and Planetary Change ,biology ,Cold season ,010604 marine biology & hydrobiology ,surface growth rings ,Growth curve (biology) ,biology.organism_classification ,age ,surface growth ring ,acetate peels ,lcsh:Q ,Chamelea gallina - Abstract
Age and growth studies provide critical data for clam fishery management. Three aging techniques, thin sections and acetate peel replicas – which involve shell sectioning – and surface growth rings were used to estimate the age and growth of Chamelea gallina populations in the mid-western Adriatic Sea. Their results were compared to identify the most reliable and least time-consuming approach. There were no significant differences between the two shell sectioning techniques (χ2 = 4.66, df = 3, p = 0.198), which were described by the same von Bertalanffy (VBF) growth curve parameters (L8 = 43.9, k = 0.26, t0 = −0.84), whereas significantly different L8 and k values were found between the two shell sectioning techniques and surface growth rings (L8: χ2 = 13.62, df = 1, p < 0.001; k: χ2 = 9.18, df = 1, p < 0.002; these statistics refer to the comparison between acetate peels and surface growth rings). The latter approach proved unreliable and error-prone, as it underestimated age and overestimated the growth rate (L8 = 26.4, k = 1.91, t0 = −0.11). Although the thin sections and acetate peel techniques both provide reliable age and growth estimates, the former approach was less time-consuming. Our analyses demonstrated that shell growth is slower in the cold season and in older specimens and that it has slowed down over the past few decades.
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- 2020
81. Deficiency of Mitochondrial Aspartate-Glutamate Carrier 1 Leads to Oligodendrocyte Precursor Cell Proliferation Defects Both In Vitro and In Vivo
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Ferdinando Palmieri, Francesca Massenzio, Marco Virgili, Miriam Capri, Alberto Danese, Carlotta Giorgi, Sabrina Petralla, Luis Emiliano Peña-Altamira, Barbara Monti, Paolo Pinton, Emanuela Profilo, Luigi Sbano, Simona N. Barile, Francesco M. Lasorsa, Mariangela Corricelli, Eleonora Poeta, Rita Ostan, Petralla S., Pena-Altamira L.E., Poeta E., Massenzio F., Virgili M., Barile S.N., Sbano L., Profilo E., Corricelli M., Danese A., Giorgi C., Ostan R., Capri M., Pinton P., Palmieri F., Lasorsa F.M., and Monti B.
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Platelet-derived growth factor ,Amino Acid Transport Systems ,endocrine system diseases ,medicine.medical_treatment ,Cellular differentiation ,Antiporters ,lcsh:Chemistry ,chemistry.chemical_compound ,Mice ,Adenosine Triphosphate ,Transforming Growth Factor beta ,Lateral Ventricles ,Receptors ,Glutamate aspartate transporter ,lcsh:QH301-705.5 ,Spectroscopy ,Membrane Potential, Mitochondrial ,Neurons ,Platelet-Derived Growth Factor ,biology ,subventricular zone ,growth factor ,Cell Differentiation ,General Medicine ,Mitochondrial ,Computer Science Applications ,Cell biology ,Mitochondria ,mitochondrial disease ,medicine.anatomical_structure ,Lactates ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction ,AGC1 deficiency ,Growth factors ,Mitochondrial disease ,Mouse model ,Subventricular zone ,Amino Acid Transport Systems, Acidic ,Animals ,Cell Line ,Cell Proliferation ,Down-Regulation ,Gene Silencing ,Oligodendrocyte Precursor Cells ,Reactive Oxygen Species ,Receptors, Transforming Growth Factor beta ,mouse model ,Membrane Potential ,Catalysis ,Article ,NO ,Inorganic Chemistry ,Precursor cell ,Neurosphere ,growth factors ,medicine ,Physical and Theoretical Chemistry ,Molecular Biology ,Growth factor ,Acidic ,Organic Chemistry ,nutritional and metabolic diseases ,Transforming growth factor beta ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,nervous system ,biology.protein - Abstract
Aspartate-Glutamate Carrier 1 (AGC1) deficiency is a rare neurological disease caused by mutations in the solute carrier family 25, member 12 (SLC25A12) gene, encoding for the mitochondrial aspartate-glutamate carrier isoform 1 (AGC1), a component of the malate&ndash, aspartate NADH shuttle (MAS), expressed in excitable tissues only. AGC1 deficiency patients are children showing severe hypotonia, arrested psychomotor development, seizures and global hypomyelination. While the effect of AGC1 deficiency in neurons and neuronal function has been deeply studied, little is known about oligodendrocytes and their precursors, the brain cells involved in myelination. Here we studied the effect of AGC1 down-regulation on oligodendrocyte precursor cells (OPCs), using both in vitro and in vivo mouse disease models. In the cell model, we showed that a reduced expression of AGC1 induces a deficit of OPC proliferation leading to their spontaneous and precocious differentiation into oligodendrocytes. Interestingly, this effect seems to be related to a dysregulation in the expression of trophic factors and receptors involved in OPC proliferation/differentiation, such as Platelet-Derived Growth Factor &alpha, (PDGF&alpha, ) and Transforming Growth Factor &beta, s (TGF&beta, s). We also confirmed the OPC reduction in vivo in AGC1-deficent mice, as well as a proliferation deficit in neurospheres from the Subventricular Zone (SVZ) of these animals, thus indicating that AGC1 reduction could affect the proliferation of different brain precursor cells. These data clearly show that AGC1 impairment alters myelination not only by acting on N-acetyl-aspartate production in neurons but also on OPC proliferation and suggest new potential therapeutic targets for the treatment of AGC1 deficiency.
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- 2019
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82. Changing paradigm to target microglia in neurodegenerative diseases: from anti-inflammatory strategy to active immunomodulation
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Marco Virgili, Barbara Monti, Emiliano Peña-Altamira, Federica Prati, Maria Laura Bolognesi, Antonio Contestabile, Francesca Massenzio, Peña-Altamira, E, Prati, F, Massenzio, F, Virgili, M, Contestabile, A, Bolognesi, Ml, and Monti, B.
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,medicine.drug_class ,Clinical Biochemistry ,Drug target ,Anti-Inflammatory Agents ,Inflammation ,Disease ,Neuroprotection ,Anti-inflammatory ,Immunomodulation ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,M2 and M1 phenotype ,Drug Discovery ,Animals ,Humans ,Medicine ,Amyotrophic lateral sclerosis ,Pharmacology ,Microglia ,business.industry ,Neurodegenerative Diseases ,medicine.disease ,Neurodegenerative diseases ,030104 developmental biology ,medicine.anatomical_structure ,Molecular Medicine ,medicine.symptom ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
INTRODUCTION: The importance of microglia in most neurodegenerative pathologies, from Parkinson's disease to amyotrophic lateral sclerosis and Alzheimer's disease, is increasingly recognized. Until few years ago, microglial activation in pathological conditions was considered dangerous to neurons due to its causing inflammation. Today we know that these glial cells also play a crucial physiological and neuroprotective role, which is altered in neurodegenerative conditions. AREAS COVERED: The neuroinflammatory hypothesis for neurodegenerative diseases has led to the trial of anti-inflammatory agents as therapeutics with largely disappointing results. New information about the physiopathological role of microglia has highlighted the importance of immunomodulation as a potential new therapeutic approach. This review summarizes knowledge on microglia as a potential therapeutic target in the most common neurodegenerative diseases, with focus on compounds directed toward the modulation of microglial immune response through specific molecular pathways. EXPERT OPINION: Here we support the innovative concept of targeting microglial cells by modulating their activity, rather than simply trying to counteract their inflammatory neurotoxicity, as a potential therapeutic approach for neurodegenerative diseases. The advantage of this therapeutic approach could be to reduce neuroinflammation and toxicity, while at the same time strengthening intrinsic neuroprotective properties of microglia and promoting neuroregeneration.
- Published
- 2015
83. Release of soluble and vesicular purine nucleoside phosphorylase from rat astrocytes and microglia induced by pro-inflammatory stimulation with extracellular ATP via P2X7 receptors
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Patricia Giuliani, Francesco Caciagli, Patrizia Di Iorio, Francesca Massenzio, Mariachiara Zuccarini, Marco Virgili, Alina Beraudi, Ilaria Mengoni, Alessandro Poli, Barbara Monti, Renata Ciccarelli, Luis Emiliano Peña-Altamira, Elisabetta Polazzi, DIP. DI BIOLOGIA EVOLUZIONISTICA SPERIMENTALE, DIPARTIMENTO DI FARMACIA E BIOTECNOLOGIE, Facolta' di SCIENZE MATEMATICHE FISICHE e NATURALI, Da definire, AREA MIN. 05 - Scienze biologiche, and Peña-Altamira LE, Polazzi E, Giuliani P, Beraudi A, Massenzio F, Mengoni I, Poli A, Zuccarini M, Ciccarelli R, Di Iorio P, Virgili M, Monti B, Caciagli F.
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0301 basic medicine ,Purine ,Programmed cell death ,Mechanism of release ,Lysosomal vesicles ,Purine nucleoside phosphorylase ,Biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Extracellular ,Secretion ,Extracellular purine nucleoside phosphorylase (PNP) ,Receptor ,Purine metabolism ,Microglia ,Cell Biology ,Molecular biology ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Brain cell cultures, Extracellular purine nucleoside phosphorylase (PNP), P2X7 receptor, Mechanism of release, Lysosomal vesicles ,P2X7 receptor ,030217 neurology & neurosurgery ,Brain cell cultures - Abstract
none 13 no Available online 20 October 2017 Purine nucleoside phosphorylase (PNP), a crucial enzyme in purine metabolism which converts ribonucleosides into purine bases, has mainly been found inside glial cells. Since we recently demonstrated that PNP is released from rat C6 glioma cells, we then wondered whether this occurs in normal brain cells. Using rat primary cultures of microglia, astrocytes and cerebellar granule neurons, we found that in basal condition all these cells constitutively released a metabolically active PNP with Km values very similar to those measured in C6 glioma cells. However, the enzyme expression/release was greater in microglia or astrocytes that in neurons. Moreover, we exposed primary brain cell cultures to pro-inflammatory agents such as lipopolysaccharide (LPS) or ATP alone or in combination. LPS alone caused an increased interleukin-1β (IL-1β) secretion mainly from microglia and no modification in the PNP release, even from neurons in which it enhanced cell death. In contrast, ATP administered alone to glial cells at high micromolar concentrations significantly stimulated the release of PNP within 1 h, an effect not modified by LPS presence, whereas IL-1β secretion was stimulated by ATP only in cells primed for 2 h with LPS. In both cases ATP effect was mediated by P2X7 receptor (P2X7R), since it was mimicked by cell exposure to Bz-ATP, an agonist of P2X7R, and blocked by cell pre-treatment with the P2X7R antagonist A438079. Interestingly, ATP-induced PNP release from glial cells partly occurred through the secretion of lysosomal vesicles in the extracellular medium. Thus, during inflammatory cerebral events PNP secretion promoted by extracellular ATP accumulation might concur to control extracellular purine signals. Further studies could elucidate whether, in these conditions, a consensual activity of enzymes downstream of PNP in the purine metabolic cascade avoids accumulation of extracellular purine bases that might concur to brain injury by unusual formation of reactive oxygen species. mixed Peña-Altamira LE, Polazzi E, Giuliani P, Beraudi A, Massenzio F, Mengoni I, Poli A, Zuccarini M, Ciccarelli R, Di Iorio P, Virgili M, Monti B, Caciagli F. Peña-Altamira LE, Polazzi E, Giuliani P, Beraudi A, Massenzio F, Mengoni I, Poli A, Zuccarini M, Ciccarelli R, Di Iorio P, Virgili M, Monti B, Caciagli F.
- Published
- 2018
84. Nutritional and Pharmacological Strategies to Regulate Microglial Polarization in Cognitive Aging and Alzheimer’s Disease
- Author
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Francesca Massenzio, Marco Virgili, Sabrina Petralla, Maria Laura Bolognesi, Barbara Monti, Emiliano Peña-Altamira, Peña-Altamira, E, Petralla, S, Massenzio, F, Virgili, M, Bolognesi, Ml, and Monti, B.
- Subjects
0301 basic medicine ,Senescence ,Aging ,Cognitive Neuroscience ,microglia ,Review ,Disease ,immunomodulation ,Neuroprotection ,lcsh:RC321-571 ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Medicine ,Dementia ,bioactive compound ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Neuroinflammation ,cognitive impairment ,bioactive compounds ,Microglia ,business.industry ,medicine.disease ,drug therapy ,nutrition ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Immunology ,Alzheimer's disease ,business ,Alzheimer’s disease ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The study of microglia, the immune cells of the brain, has experienced a renaissance after the discovery of microglia polarization. In fact, the concept that activated microglia can shift into the M1 pro-inflammatory or M2 neuroprotective phenotypes, depending on brain microenvironment, has completely changed the understanding of microglia in brain aging and neurodegenerative diseases. Microglia polarization is particularly important in aging since an increased inflammatory status of body compartments, including the brain, has been reported in elderly people. In addition, inflammatory markers, mainly derived from activated microglia, are widely present in neurodegenerative diseases. Microglial inflammatory dysfunction, also linked to microglial senescence, has been extensively demonstrated and associated with cognitive impairment in neuropathological conditions related to aging. In fact, microglia polarization is known to influence cognitive function and has therefore become a main player in neurodegenerative diseases leading to dementia. As the life span of human beings increases, so does the prevalence of cognitive dysfunction. Thus, therapeutic strategies aimed to modify microglia polarization are currently being developed. Pharmacological approaches able to shift microglia from M1 pro-inflammatory to M2 neuroprotective phenotype are actually being studied, by acting on many different molecular targets, such as glycogen synthase kinase-3 (GSK3) β, AMP-activated protein kinase (AMPK), histone deacetylases (HDACs), etc. Furthermore, nutritional approaches can also modify microglia polarization and, consequently, impact cognitive function. Several bioactive compounds normally present in foods, such as polyphenols, can have anti-inflammatory effects on microglia. Both pharmacological and nutritional approaches seem to be promising, but still need further development. Here we review recent data on these approaches and propose that their combination could have a synergistic effect to counteract cognitive aging impairment and Alzheimer’s disease (AD) through immunomodulation of microglia polarization, i.e., by driving the shift of activated microglia from the pro-inflammatory M1 to the neuroprotective M2 phenotype.
- Published
- 2017
85. Down-regulation of the mitochondrial aspartate-glutamate carrier isoform 1 AGC1 inhibits proliferation and N-acetylaspartate synthesis in Neuro2A cells
- Author
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Luigi Palmieri, Alessandra Castegna, Emanuela Profilo, Luis Emiliano Peña-Altamira, Sabrina Petralla, Massimo Zeviani, Mariangela Corricelli, Vito Porcelli, Barbara Monti, Giuseppe Fiermonte, Ferdinando Palmieri, Paolo Pinton, Giulia Giannuzzi, Luigi Sbano, Alberto Danese, Marco Virgili, Carlotta Giorgi, Carlo Viscomi, Francesca Massenzio, Erika M. Palmieri, Francesco M. Lasorsa, Gennaro Agrimi, Profilo, E, Peña-Altamira, Le, Corricelli, M, Castegna, A, Danese, A, Agrimi, G, Petralla, S, Giannuzzi, G, Porcelli, V, Sbano, L, Viscomi, C, Massenzio, F, Palmieri, Em, Giorgi, C, Fiermonte, G, Virgili, M, Palmieri, L, Zeviani, M, Pinton, P, Monti, B, Palmieri, F, and Lasorsa, Fm.
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Mitochondrial Diseases ,Amino Acid Transport Systems ,Amino Acid Transport Systems, Acidic ,AGC1 deficiency ,Brain hypomyelination ,Mitochondrial aspartate/glutamate carrier ,N-Acetylaspartate synthesis ,Neurodegenerative disorders ,Antiporters ,Aspartic Acid ,Cell Line ,Hereditary Central Nervous System Demyelinating Diseases ,Humans ,Mitochondrial Proteins ,Neurons ,Psychomotor Disorders ,Cell Proliferation ,Down-Regulation ,Biology ,Mitochondrion ,NO ,03 medical and health sciences ,Myelin ,Downregulation and upregulation ,Internal medicine ,medicine ,Glutamate aspartate transporter ,Molecular Medicine ,Molecular Biology ,brain hypomyelination ,Cell growth ,Acidic ,Glutamate receptor ,N-acetylaspartate synthesi ,Glutamine ,Cytosol ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,nervous system ,neurodegenerative disorders ,biology.protein - Abstract
The mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) catalyzes a Ca2+-stimulated export of aspartate to the cytosol in exchange for glutamate, and is a key component of the malate-aspartate shuttle which transfers NADH reducing equivalents from the cytosol to mitochondria. By sustaining the complete glucose oxidation, AGC1 is thought to be important in providing energy for cells, in particular in the CNS and muscle where this protein is mainly expressed. Defects in the AGC1 gene cause AGC1 deficiency, an infantile encephalopathy with delayed myelination and reduced brain N-acetylaspartate (NAA) levels, the precursor of myelin synthesis in the CNS. Here, we show that undifferentiated Neuro2A cells with down-regulated AGC1 display a significant proliferation deficit associated with reduced mitochondrial respiration, and are unable to synthesize NAA properly. In the presence of high glutamine oxidation, cells with reduced AGC1 restore cell proliferation, although oxidative stress increases and NAA synthesis deficit persists. Our data suggest that the cellular energetic deficit due to AGC1 impairment is associated with inappropriate aspartate levels to support neuronal proliferation when glutamine is not used as metabolic substrate, and we propose that delayed myelination in AGC1 deficiency patients could be attributable, at least in part, to neuronal loss combined with lack of NAA synthesis occurring during the nervous system development.
- Published
- 2017
86. Evidence for purine nucleoside phosphorylase (PNP) release from rat C6 glioma cells
- Author
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Michel P. Rathbone, Marco Virgili, Francesco Caciagli, Elisabetta Polazzi, Silvana Buccella, Barbara Monti, Mariachiara Zuccarini, Luis Emiliano Peña-Altamira, Renata Ciccarelli, Alessandro Poli, Patricia Giuliani, Patrizia Di Iorio, Giuliani, P, Zuccarini, M, Buccella, S, Peña-Altamira, Le, Polazzi, E, Virgili, M, Monti, B, Poli, A, Rathbone, Mp, Di Iorio, P, Ciccarelli, R, and Caciagli, F.
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0301 basic medicine ,Purine ,modulation of enzyme activity ,Purine nucleoside phosphorylase ,Biology ,Biochemistry ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Cell Line, Tumor ,medicine ,Extracellular ,Animals ,Nucleotide ,extracellular PNP ,Purine metabolism ,chemistry.chemical_classification ,Glioma ,Xanthine ,Adenosine ,Rats ,purine metabotropic receptor ,030104 developmental biology ,rat C6 glioma cells ,chemistry ,Purine-Nucleoside Phosphorylase ,purine release ,Intracellular ,medicine.drug - Abstract
Intracellular purine turnover is mainly oriented to preserving the level of triphosphate nucleotides, fundamental molecules in vital cell functions that, when released outside cells, act as receptor signals. Conversely, high levels of purine bases and uric acid are found in the extracellular milieu, even in resting conditions. These compounds could derive from nucleosides/bases that, having escaped to cell reuptake, are metabolized by extracellular enzymes similar to the cytosolic ones. Focusing on purine nucleoside phosphorylase (PNP) that catalyzes the reversible phosphorolysis of purine (deoxy)-nucleosides/bases, we found that it is constitutively released from cultured rat C6 glioma cells into the medium, and has a molecular weight and enzyme activity similar to the cytosolic enzyme. Cell exposure to 10 μM ATP or GTP increased the extracellular amount of all corresponding purines without modifying the levels/activity of released PNP, whereas selective activation of ATP P2Y1 or adenosine A2A metabotropic receptors increased PNP release and purine base formation. The reduction to 1% in oxygen supply (2 h) to cells decreased the levels of released PNP, leading to an increased presence of extracellular nucleosides and to a reduced formation of xanthine and uric acid. Conversely, 2 hour-cell re-oxygenation enhanced the extracellular amounts of both PNP and purine bases. Thus, hypoxia and re-oxygenation modulated in opposite manner the PNP release/activity and, thereby, the extracellular formation of purine metabolism end-products. In conclusion, extracellular PNP and likely other enzymes deputed to purine base metabolism are released from cells, contributing to the purinergic system homeostasis and exhibiting an important pathophysiological role. This article is protected by copyright. All rights reserved.
- Published
- 2016
87. Zinc supplementation in rats impairs hippocampal-dependent memory consolidation and dampens post-traumatic recollection of stressful event
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Barbara Monti, Emiliano Peña-Altamira, Antonio Contestabile, Marco Virgili, Contestabile, A, Peña-Altamira, E, Virgili, M, and Monti, B.
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0301 basic medicine ,Male ,Contextual fear conditioning ,MAP Kinase Signaling System ,Neurogenesis ,Hippocampus ,Hippocampal formation ,Developmental psychology ,Stress Disorders, Post-Traumatic ,03 medical and health sciences ,Glycogen Synthase Kinase 3 ,0302 clinical medicine ,Conditioning, Psychological ,medicine ,Animals ,Pharmacology (medical) ,Effects of sleep deprivation on cognitive performance ,Rats, Wistar ,Phosphorylation ,Biological Psychiatry ,Memory Consolidation ,Pharmacology ,Recall ,Long-term treatment ,Cognition ,Fear ,Inhibitory avoidance ,medicine.disease ,Rats ,Trace Elements ,GSK-3ß ,Psychiatry and Mental health ,Zinc ,030104 developmental biology ,Neurology ,Synaptic plasticity ,Dietary Supplements ,Zinc deficiency ,Wounds and Injuries ,Memory consolidation ,Neurology (clinical) ,Psychology ,Neuroscience ,030217 neurology & neurosurgery ,Stress, Psychological - Abstract
Zinc is a trace element important for synaptic plasticity, learning and memory. Zinc deficiency, both during pregnancy and after birth, impairs cognitive performance and, in addition to memory deficits, also results in alterations of attention, activity, neuropsychological behavior and motor development. The effects of zinc supplementation on cognition, particularly in the adult, are less clear. We demonstrate here in adult rats, that 4 week-long zinc supplementation given by drinking water, and approximately doubling normal daily intake, strongly impairs consolidation of hippocampal-dependent memory, tested through contextual fear conditioning and inhibitory avoidance. Furthermore, the same treatment started after memory consolidation of training for the same behavioral tests, substantially dampens the recall of the stressful event occurred 4 weeks before. A molecular correlate of the amnesic effect of zinc supplementation is represented by a dysregulated function of GSK-3s in the hippocampus, a kinase that participates in memory processes. The possible relevance of these data for humans, in particular regarding post-traumatic stress disorders, is discussed in view of future investigation.
- Published
- 2016
88. Neuronal Regulation of Neuroprotective Microglial Apolipoprotein E Secretion in Rat In Vitro Models of Brain Pathophysiology
- Author
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Marco Virgili, Elisabetta Polazzi, Barbara Monti, Emiliano Peña-Altamira, Francesca Massenzio, Ilaria Mengoni, Sabrina Petralla, Polazzi, E, Mengoni, I, Peña-Altamira, E, Massenzio, F, Virgili, M, Petralla, S, and Monti, B.
- Subjects
Apolipoprotein E ,Lipopolysaccharide ,Cerebellar granule neuron ,Enzyme-Linked Immunosorbent Assay ,Biology ,In Vitro Techniques ,Real-Time Polymerase Chain Reaction ,Transfection ,Neuroprotection ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Apolipoproteins E ,Serine ,medicine ,Gene silencing ,Animals ,Secretion ,RNA, Small Interfering ,Rats, Wistar ,Receptor ,Cells, Cultured ,Chromatography, High Pressure Liquid ,Neurons ,Brain Diseases ,Microglia ,Glutamate receptor ,General Medicine ,Immunohistochemistry ,Coculture ,Coculture Techniques ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,nervous system ,Neurology ,chemistry ,Release ,Culture Media, Conditioned ,lipids (amino acids, peptides, and proteins) ,Neurology (clinical) ,Neuroscience - Abstract
Apolipoprotein E (ApoE) is mainly secreted by glial cells and is involved in many brain functions, including neuronal plasticity, β-amyloid clearance, and neuroprotection. Microglia--the main immune cells of the brain--are one source of ApoE, but little is known about the physiologic regulation of microglial ApoE secretion by neurons and whether this release changes under inflammatory or neurodegenerative conditions. Using rat primary neural cell cultures, we show that microglia release ApoE through a Golgi-mediated secretion pathway and that ApoE progressively accumulates in neuroprotective microglia-conditioned medium. This constitutive ApoE release is negatively affected by microglial activation both with lipopolysaccharide and with ATP. Microglial ApoE release is stimulated by neuron-conditioned media and under coculture conditions. Neuron-stimulated microglial ApoE release is mediated by serine and glutamate through N-methyl-D-aspartate receptors and is differently regulated by activation states (i.e. lipopolysaccharide vs ATP) and by 6-hydroxydopamine. Microglial ApoE silencing abrogated protection of cerebellar granule neurons against 6-hydroxydopamine toxicity in cocultures, indicating that microglial ApoE release is neuroprotective. Our findings shed light on the reciprocal cross-talk between neurons and microglia that is crucial for normal brain functions. They also open the way for the identification of possible pharmacologic targets that can modulate neuroprotective microglial ApoE release under pathologic conditions.
- Published
- 2015
89. Regional and temporal alterations of ODC/polyamine system during ALS-like neurodegenerative motor syndrome in G93A transgenic mice
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Marco Virgili, Emiliano Peña-Altamira, Antonio Contestabile, Christophe Crochemore, VIRGILI M., CROCHEMORE C., PENA-ALTAMIRA E., and CONTESTABILE A.
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Central Nervous System ,medicine.medical_specialty ,SOD1 ,Spermine ,Mice, Transgenic ,Biology ,Ornithine decarboxylase ,Mice ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,MOTOR NEURON DISEASE ,TRANSGENIC MICE ,Amyotrophic Lateral Sclerosis ,Biogenic Polyamines ,Neurodegeneration ,Cell Biology ,Motor neuron ,medicine.disease ,ORNITHINE DECARBOXYLASE ,POLYAMINES ,Spermidine ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Biochemistry ,Putrescine ,Polyamine ,SPINAL CORD - Abstract
Natural polyamines (putrescine, spermidine and spermine) are ubiquitous molecules known to regulate a number of physiological processes and suspected to play a role also in various pathological conditions. Changes in polyamine levels and in their biosynthetic enzymes have been described for some neurodegenerative diseases but the available data are incomplete and somewhat contradictory. We report here alterations of the key enzyme of the polyamine pathway, ornithine decarboxylase (ODC) catalytic activity and polyamine levels in different CNS areas from SOD1 G39A transgenic mice, an animal model for amyotrophic lateral sclerosis (ALS). ODC catalytic activity, was found significantly increased both in the cervical and lumbar spinal cord and, to a lesser extent in the brain stem of transgenic mice at a symptomatic stage of the disease (125 day-old mice), while no differences were present at a pre-symptomatic stage (55 day-old mice). In parallel with the increase of ODC activity putrescine levels were several times increased in both cervical and lumbar spinal cord and in the brain stem of 125 day-old SOD1 G39A mice. Higher order polyamines were not increased except for a significant increase of spermidine in the cervical spinal cord. The present data demonstrate considerable alterations of the ODC/polyamine system in a reliable animal model of ASL, consistent with their role in neurodegeneration and in particular in motor neuron diseases.
- Published
- 2006
90. Neurochemical correlates of differential neuroprotection by long-term dietary creatine supplementation
- Author
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Christophe Crochemore, Marco Virgili, Antonio Contestabile, Emiliano Peña-Altamira, Pena-Altamira E., Crochemore C., Virgili M., and Contestabile A.
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Male ,medicine.medical_specialty ,Neurotoxins ,Excitotoxicity ,Mice, Transgenic ,Biology ,Creatine ,medicine.disease_cause ,Neuroprotection ,Time ,Mice ,chemistry.chemical_compound ,Neurochemical ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Cholinergic neuron ,Ibotenic Acid ,Molecular Biology ,Basal forebrain ,Cell Death ,Glutamate Decarboxylase ,General Neuroscience ,Amyotrophic Lateral Sclerosis ,Brain ,Neurodegenerative Diseases ,Acetylcholine ,Corpus Striatum ,Rats ,Survival Rate ,Neuroprotective Agents ,Treatment Outcome ,Endocrinology ,Cholinergic Fibers ,chemistry ,Basal Nucleus of Meynert ,Dietary Supplements ,Cholinergic ,Neurology (clinical) ,Biomarkers ,Ibotenic acid ,Developmental Biology - Abstract
Dietary supplementation with creatine has proven to be beneficial in models of acute and chronic neurodegeneration. We report here data on the neurochemical correlates of differential protection of long-term creatine supplementation in two models of excitotoxicity in rats, as well as in the mouse model for ALS (G93A mice). In rats, the fall in cholinergic and GABAergic markers due to the excitotoxic death of intrinsic neurons caused by intrastriatal infusion of the neurotoxin, ibotenic acid, was significantly prevented by long-term dietary supplementation with creatine. On the contrary, creatine was unable to recover a cholinergic marker in the cortex of rats subjected to the excitotoxic death of the cholinergic basal forebrain neurons. In G93A mice, long-term creatine supplementation marginally but significantly increased mean lifespan, as previously observed by others, and reverted the cholinergic deficit present in some forebrain areas at an intermediate stage of the disease. In both rats and mice, creatine supplementation increased the activity of the GABAergic enzyme, glutamate decarboxylase, in the striatum but not in other brain regions. The present data point at alterations of neurochemical parameters marking specific neuronal populations, as a useful way to evaluate neuroprotective effects of long-term creatine supplementation in animal models of neurodegeneration.
- Published
- 2005
91. Disease-related regressive alterations of forebrain cholinergic system in SOD1 mutant transgenic mice
- Author
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Antonio Contestabile, Barbara Monti, Emiliano Peña-Altamira, Christophe Crochemore, Marco Virgili, CROCHEMORE C., PENA-ALTAMIRA E., VIRGILI M., MONTI B., and CONTESTABILE A.
- Subjects
Male ,CORTEX ,medicine.medical_specialty ,Central nervous system ,Down-Regulation ,Hippocampus ,Mice, Transgenic ,Biology ,Choline ,Choline O-Acetyltransferase ,Mice ,Cellular and Molecular Neuroscience ,Superoxide Dismutase-1 ,Pregnancy ,Internal medicine ,Neural Pathways ,medicine ,Animals ,Cholinergic neuron ,Maternal-Fetal Exchange ,gamma-Aminobutyric Acid ,MOTOR NEURON DISEASE ,Cerebral Cortex ,Motor Neurons ,Basal forebrain ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,Cell Biology ,Motor neuron ,Choline acetyltransferase ,Acetylcholine ,Disease Models, Animal ,Treatment Outcome ,medicine.anatomical_structure ,Endocrinology ,Cholinergic Fibers ,Spinal Cord ,nervous system ,Basal Nucleus of Meynert ,Dietary Supplements ,Nerve Degeneration ,Forebrain ,CHOLINERGIC SYSTEMS ,Cholinergic ,Female ,Brain Stem - Abstract
Transgenic mice carrying the human mutated SOD1 gene with a glycine/alanine substitution at codon 93 (G93A) are a widely used model for the fatal human disease amyotrophic lateral sclerosis (ALS). In these transgenic mice, we carried out a neurochemical study not only restricted to the primarily affected regions, the cervical and lumbar segments of the spinal cord, but also to several other brain regions. At symptomatic (110 and 125 days of age), but not at pre-symptomatic (55 days of age) stages, we found significant decreases in catalytic activity of the cholinergic enzyme, choline acetyltransferase (ChAT) in the hippocampus, olfactory cortex and fronto-parietal cortex. In parallel, we observed a decreased number of basal forebrain cholinergic neurons projecting to these areas. No alterations of the cholinergic markers were noticed in the striatum and the cerebellum. A widespread marker for GABAergic neurons, glutamate decarboxylase (GAD), was unaffected in all the areas examined. Alteration of cholinergic markers in forebrain areas was paralleled by concomitant alterations in the spinal cord and brainstem, as a consequence of progressive apoptotic elimination of cholinergic motor neuron. Gestational supplementation of choline, while able to result in long-term enhancement of cholinergic activity, did not improve transgenic mice lifespan nor counteracted cholinergic impairment in brain regions and spinal cord.
- Published
- 2005
92. Alterations of markers related to synaptic function in aging rat brain, in normal conditions or under conditions of long-term dietary manipulation
- Author
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Antonio Contestabile, Marco Virgili, Barbara Monti, MONTI B., VIRGILI M., and CONTESTABILE A.
- Subjects
Male ,Senescence ,Aging ,medicine.medical_specialty ,Blotting, Western ,Central nervous system ,Biology ,Ornithine Decarboxylase ,Receptors, N-Methyl-D-Aspartate ,Choline O-Acetyltransferase ,Acetylcysteine ,Cellular and Molecular Neuroscience ,Neurochemical ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Receptor ,Brain Chemistry ,Body Weight ,Glutamate receptor ,Brain ,Free Radical Scavengers ,Cell Biology ,Diet ,Rats ,Endocrinology ,medicine.anatomical_structure ,Spinal Cord ,Synapses ,Cholinergic ,GABAergic ,Biomarkers ,Densitometry ,medicine.drug - Abstract
Neurochemical alterations of markers related to synaptic function are potential candidates for age-related impairment of brain function and cognition. The process of aging, including brain aging, can be counteracted to some degree by maintaining animals in long-term conditions of caloric restriction, or supplementing their diet with antioxidant substances. We report here that the age-related decline of the cholinergic and GABAergic systems, that takes place in some CNS regions of aged rats, is not affected by maintaining them under conditions of dietary restriction and, therefore, of reduced calorie intake, from the 12th to the 30th month of age. We also notice the same lack of effect by adding, during the same period, the aging rat diet with the potential antioxidant substance, N-acetylcysteine (NAC). The same dietary manipulations are also unable to counteract the derangement of the first step of the main biosynthetic pathway for polyamines, putative neuromodulators in the CNS, that occurs in the aged spinal cord. Some age-related alterations in the expression of different subunits of the NMDA-type glutamate receptors in some CNS regions of aged rats were instead, at least in some cases, counteracted by long-term dietary manipulation.
- Published
- 2004
93. Josep Pla. viatge a l’amèrica del sud (1957) De les col·laboracions a la revista «destino» al volum En mar (1971)
- Author
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Pérez Buendia, Rosa M., Gallofré Virgili, M. Josepa, and Universitat Autònoma de Barcelona. Departament d'Antropologia Social i de Prehistòria
- Subjects
Ciències Humanes ,Josep Pla - Abstract
This paper is the result of the research done for the study of Josep Pla’s Viatge a l’Amèrica del Sud (1957), from the volume En Mar (OC 18) 1971, made up from his collaborations for the magazine Destino. In this book, the author presents, with the structure of a diary, the experiences of the trip he made for the magazine between December 1957 and March 1958, and which were published as "Cartas" and articles in the section "Calendario sin fechas”" between January and July 1958. This study has its origins in the interest to show some of the literary projects resulting from the trips Pla made between 1956 and 1960 for the magazine Destino, projects which were already introduced in L’aventura breu i meravellosa com un foc d’encenalls (Josep Pla’s collaborations for Destino, 1956-1960), in 2008, a piece of work for the Master in Catalan Studies: language and Literature and its applications, written by Rosa M. Perez Buendia, the author of this thesis. An important part of the investigation focuses on the analysis of the material for the press which Pla chose, organized, revised and rewrote to develop a story based on a real journey. In the first place, we present the articles published in Destino: an analysis according to the contents and the literary vision of these writings. Also, by comparing them with the original manuscripts, we take into consideration the role of the correctors in the final product. Next, there is an approach to how the book was actually made, referring to the texts Pla had already published and those which had been created for the occasion. As for the texts from Destino, we study which of them the author chose and the order in which they appear in the diary, because, unlike the reports, they followed the route of the voyage made in 1958. We also examine the way they were presented in the book: either reworded or as a report. Regarding the newly created material, we suggest the existence of a travel journal. Finally, through the original manuscripts, we have collected data on the role of editors in the final product. Last but not least, there is the literary study of the book Viatge a l’Amèrica del Sud (1957) which focuses on the newly created diary, taking also into consideration part of what has been analyzed with respect to the texts from Destino and its shaping into a diary. In this paper, apart from the actual study of a book based on Pla’s collaborations for Destino, we raise several questions about the relationship between the writer and the press, specifically the magazine Destino: the conditions under he worked, how he worked and what the relationship with the owner of the magazine, Josep Verges, was like. We also mention other aspects, such as the projects during this period, especially those which refer to the publisher Selecta and the relationship with the publisher Joseph M. Cruzet. We also take into account the political context, both at the time of the trip and at the time when the book was published, in 1971.
- Published
- 2014
94. Long-term dietary administration of valproic acid does not affect, while retinoic acid decreases, the lifespan of G93A mice, a model for amyotrophic lateral sclerosis
- Author
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Cristophe Crochemore, Donatella Canistro, Moreno Paolini, Emiliano Peña-Altamira, Antonio Contestabile, Barbara Bonamassa, Marco Virgili, Crochemore C., Virgili M., Bonamassa B., Canistro D., Pena-Altamira E., Paolini M., and Contestabile A.
- Subjects
Male ,medicine.medical_specialty ,Life span, amyotrophic lateral sclerosis, mice ,Physiology ,GABA Agents ,Central nervous system ,Retinoic acid ,Gene Dosage ,Antineoplastic Agents ,Mice, Transgenic ,Tretinoin ,Choline O-Acetyltransferase ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Mice ,Life Expectancy ,Superoxide Dismutase-1 ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,Cholinergic neuron ,Amyotrophic lateral sclerosis ,Valproic Acid ,business.industry ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,Motor neuron ,medicine.disease ,Spinal cord ,Animal Feed ,Lumbar Spinal Cord ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Nerve Degeneration ,Acetylcholinesterase ,Female ,Neurology (clinical) ,business ,Neuroscience ,medicine.drug - Abstract
Mice bearing the mutated gene for Cu/Zn superoxide dismutase (G93A) are a good model for human amyotrophic lateral sclerosis (ALS). They develop progressive limb paralysis paralleled by loss of motor neurons of the cervical and lumbar spinal cord, which starts at 3-3.5 months of age and ends with death at 4-5 months. Several treatments have been attempted to delay clinical symptoms and to extend lifespan, and some have had modest beneficial effects. One such treatment, based on long-term administration of valproic acid (VPA), resulted in controversial results. We report here that, while dietary supplementation with high VPA dosage slows down motor neuron death, as assessed by measurement of a specific marker for cholinergic neurons in the spinal cord, it has no significant effect on lifespan. Recently, the hypothesis has been put forward that a deficiency of retinoic acid (RA) and its signaling may have a role in ALS. We report that long-term dietary supplementation with RA has no effect on the decrease of the cholinergic marker in the spinal cord, but it significantly shortens lifespan of G93A mice.
- Published
- 2009
95. Valproic acid is neuroprotective in the rotenone rat model of Parkinson's disease: involvement of alpha-synuclein
- Author
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Valentina Gatta, Marco Virgili, Barbara Monti, Francesca Piretti, Simonetta S. Raffaelli, Antonio Contestabile, Monti B., Gatta V., Piretti F., Raffaelli S., Virgili M., and Contestabile A.
- Subjects
Male ,Insecticides ,Dopamine ,Substantia nigra ,Striatum ,DNA Fragmentation ,Biology ,Pharmacology ,Toxicology ,Neuroprotection ,Drug Administration Schedule ,Histone Deacetylases ,chemistry.chemical_compound ,Rotenone ,Animals ,Immunoprecipitation ,Parkinson Disease, Secondary ,Rats, Wistar ,Histone H3 acetylation ,Chromatography, High Pressure Liquid ,Analysis of Variance ,Tyrosine hydroxylase ,Cell Death ,General Neuroscience ,Valproic Acid ,Dopaminergic ,Brain ,Rats ,Molecular Weight ,Disease Models, Animal ,Neuroprotective Agents ,nervous system ,chemistry ,Gene Expression Regulation ,alpha-Synuclein ,lipids (amino acids, peptides, and proteins) ,Histone deacetylase activity - Abstract
Valproic acid (VPA), an established antiepileptic and antimanic drug, has recently emerged as a promising neuroprotective agent. Among its many cellular targets, VPA has been recently demonstrated to be an effective inhibitor of histone deacetylases. Accordingly, we have adopted a schedule of dietary administration (2% VPA added to the chow) that results in a significant inhibition of histone deacetylase activity and in an increase of histone H3 acetylation in brain tissues of 4 weeks-treated rats. We have tested this schedule of VPA treatment in an animal model of Parkinson's disease (PD), in which degeneration of nigro-striatal dopaminergic neurons is obtained through sub-chronic administration of the mitochondrial toxin, rotenone, via osmotic mini pumps implanted to rats. The decrease of the dopaminergic marker tyrosine hydroxylase in substantia nigra and striatum caused by 7 days toxin administration was prevented in VPA-fed rats. VPA treatment also significantly counteracted the death of nigral neurons and the 50% drop of striatal dopamine levels caused by rotenone administration. The PD-marker protein alpha-synuclein decreased, in its native form, in substantia nigra and striatum of rotenone-treated rats, while monoubiquitinated alpha-synuclein increased in the same regions. VPA treatment counteracted both these alpha-synuclein alterations. Furthermore, monoubiquitinated alpha-synuclein increased its localization in nuclei isolated from substantia nigra of rotenone-treated rats, an effect also prevented by VPA treatment. Nuclear localization of alpha-synuclein has been recently described in some models of PD and its neurodegenerative effect has been ascribed to histone acetylation inhibition. Thus, the ability of VPA to increase histone acetylation is a novel candidate mechanism for its neuroprotective action.
- Published
- 2008
96. Alpha-synuclein protects cerebellar granule neurons against 6-hydroxydopamine-induced death
- Author
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MONTI, BARBARA, POLAZZI, ELISABETTA, VIRGILI, MARCO, CONTESTABILE, ANTONIO, Batti L, Crochemore C, Monti B, Polazzi E, Batti L, Crochemore C, Virgili M, and Contestabile A.
- Subjects
nervous system ,nervous system diseases - Abstract
The physiological role of alpha-synuclein, a protein found enriched in intraneuronal deposits characterizing Parkinson's disease, is debated. While its aggregation is usually considered linked to neuropathology, its normal function may be related to fundamental processes of synaptic transmission and plasticity. By using antisense oligonucleotide strategy, we report in this study that alpha-synuclein silencing in cultured cerebellar granule cells results in widespread death of these neurons, thus demonstrating an essential pro-survival role of the protein towards primary neurons. To study alpha-synuclein expression and processing in a Parkinson's disease model of neurotoxicity, we exposed differentiated cultures of cerebellar granule neurons to toxic concentrations of 6-hydroxydopamine (6-OHDA). This resulted in neuronal death accompanied by a decrease of the monomeric form of alpha-synuclein, which was due to both decreased synthesis of the protein and its increased mono-ubiquitination accompanied by nuclear translocation. The essential neuroprotective role of alpha-synuclein was confirmed by the fact that subchronic valproate treatment, which increases alpha-synuclein expression and prevents its nuclear translocation in cerebellar granule cells exposed to 6-OHDA, significantly protected these neurons from 6-OHDA insult. In agreement with the pro-survival role of alpha-synuclein in this model, subtoxic concentrations of alpha-synuclein antisense oligonucleotides, aggravated 6-OHDA toxicity towards granule neurons. Our results demonstrate that normal alpha-synuclein expression is essential for the viability of primary neurons and that its pro-survival role is abolished in 6-OHDA neurotoxic challenge. These results are relevant to more precisely define the role of alpha-synuclein in neuronal cells and to better understand its putative involvement in neurodegeneration.
- Published
- 2007
97. Evaluation and quantification of shell damage and survival of the striped venus clam (Chamelea gallina) harvested by hydraulic dredges.
- Author
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Bargione G, Barone G, Virgili M, and Lucchetti A
- Subjects
- Animals, Humans, Seafood, Bivalvia physiology
- Abstract
The impact of hydraulic dredging on Chamelea gallina populations in the mid-western Adriatic Sea was assessed by evaluating and quantifying the damage exerted on harvested (non-sieved) and sorted (sieved by the mechanical vibrating sieve: commercial or discarded) individuals and by estimating the survival probability of discarded clams. The results showed that: i) dredging had a higher impact on determining shell damage than the mechanical vibrating sieve, ii) damage probability was strongly associated with shell length and in discard samples the effect of the shell length was greater due to the longer time spent by the individuals inside in the vibrating sieve before being rejected to the sea, iii) the survivability of the entire discarded fraction of clams was high. The findings support the Regulation (CE) 1380/2013 which foresees that discards from the Venus clam fishery must be returned to the sea and shall not be landed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
98. Every animal matters! Evaluating the selectivity of a Mediterranean bottom trawl fishery from a species community perspective.
- Author
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Petetta A, Herrmann B, Li Veli D, Virgili M, De Marco R, and Lucchetti A
- Subjects
- Animals, Fisheries, Fishes, Gadiformes, Flounder
- Abstract
Bottom trawl fisheries often catch several species simultaneously. However, most studies addressing the catch performance and selectivity of a specific trawl focus on a few commercially important or most vulnerable species requiring management measures. By contrast, the present study considers the multispecies nature of Mediterranean bottom trawl fisheries through a holistic approach that accounts for the full species community in the catches. Specifically, we evaluated and compared the catch performance of the two codends allowed for this fishery, made of 40 mm square (SM40) and 50 mm diamond (DM50) meshes. Results showed that 50 and 80% of the catch in weight and count numbers, respectively, consisted of species without commercial value, demonstrating that large proportions of the catch are not considered when using the existing approach to evaluate the ecological impact of the fishing activity. Significant differences in catch profiles between the two codends were observed, especially for two commercial flatfish species, Arnoglossus laterna and Citharus linguatula, with larger contributions in the SM40. Further, the SM40 codend had a significantly higher retention, compared to DM50 codend, for specific sizes of Merluccius merluccius and Mullus barbatus. The outcomes of the study can be useful for the Mediterranean bottom trawl fisheries management., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Petetta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
- Full Text
- View/download PDF
99. Histone Acetylation Defects in Brain Precursor Cells: A Potential Pathogenic Mechanism Causing Proliferation and Differentiation Dysfunctions in Mitochondrial Aspartate-Glutamate Carrier Isoform 1 Deficiency.
- Author
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Poeta E, Petralla S, Babini G, Renzi B, Celauro L, Magnifico MC, Barile SN, Masotti M, De Chirico F, Massenzio F, Viggiano L, Palmieri L, Virgili M, Lasorsa FM, and Monti B
- Abstract
Mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) deficiency is an ultra-rare genetic disease characterized by global hypomyelination and brain atrophy, caused by mutations in the SLC25A12 gene leading to a reduction in AGC1 activity. In both neuronal precursor cells and oligodendrocytes precursor cells (NPCs and OPCs), the AGC1 determines reduced proliferation with an accelerated differentiation of OPCs, both associated with gene expression dysregulation. Epigenetic regulation of gene expression through histone acetylation plays a crucial role in the proliferation/differentiation of both NPCs and OPCs and is modulated by mitochondrial metabolism. In AGC1 deficiency models, both OPCs and NPCs show an altered expression of transcription factors involved in the proliferation/differentiation of brain precursor cells (BPCs) as well as a reduction in histone acetylation with a parallel alteration in the expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, histone acetylation dysfunctions have been dissected in in vitro models of AGC1 deficiency OPCs (Oli-Neu cells) and NPCs (neurospheres), in physiological conditions and following pharmacological treatments. The inhibition of HATs by curcumin arrests the proliferation of OPCs leading to their differentiation, while the inhibition of HDACs by suberanilohydroxamic acid (SAHA) has only a limited effect on proliferation, but it significantly stimulates the differentiation of OPCs. In NPCs, both treatments determine an alteration in the commitment toward glial cells. These data contribute to clarifying the molecular and epigenetic mechanisms regulating the proliferation/differentiation of OPCs and NPCs. This will help to identify potential targets for new therapeutic approaches that are able to increase the OPCs pool and to sustain their differentiation toward oligodendrocytes and to myelination/remyelination processes in AGC1 deficiency, as well as in other white matter neuropathologies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Poeta, Petralla, Babini, Renzi, Celauro, Magnifico, Barile, Masotti, De Chirico, Massenzio, Viggiano, Palmieri, Virgili, Lasorsa and Monti.)
- Published
- 2022
- Full Text
- View/download PDF
100. Chamelea gallina reproductive biology and Minimum Conservation Reference Size: implications for fishery management in the Adriatic Sea.
- Author
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Bargione G, Donato F, Barone G, Virgili M, Penna P, and Lucchetti A
- Abstract
Background: The striped venus clam Chamelea gallina is an economically important species in Adriatic Sea fisheries. The use of hydraulic dredging for its catch has a long history in Italy and its management faced several stages of development in the last 40 years. A great effort has been made in the past two decades to move from poorly or weakly managed fisheries to a well-structured co-management system to improve the sustainability of this fishery. However, a prerequisite for appropriate resource management is a sound knowledge of the biology and reproductive strategy of the species., Results: We investigated three major biological features- the gametogenic cycle, size at sexual maturity and partial fecundity - by microscopic, histological and video analysis techniques. We demonstrated that its breeding season is driven by rises in seawater temperature and chlorophyll-a concentration and that its spawning period lasted from March to September. Size at sexual maturity was reached very early in the life cycle. As regards partial fecundity - the number of mature oocytes potentially released by females with ripe gonads in a single release event - varied in relation to size. Nevertheless, the reduction on the Minimum Conservation Reference Size (MCRS) from 25 to 22 mm (Delegated Regulation (EU) 2020/2237) lead to a 40% reduction in the number of emitted eggs., Conclusions: We suggest that the ability of Adriatic clam stocks to withstand the strong fishing pressure of the past 40 years and the present one is due to their high reproductive potential and multiple spawning events combined with the effect of management measures (closed areas/seasons, quota, MCRS) and technical constraints on the gear and the sieve on board. Moreover, since the reduced MCRS for Venus shells is still larger than the size at maturity, it will probably not be detrimental to the reproductive capacity of the stock., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
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