11 results on '"Filpa V"'
Search Results
2. Gut dismotility after catechol-O-methyltransferase and dopamine transporter genetic reduction in mice: implication in irritable bowel syndrome pathogenesis
- Author
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Caputi, Valentina, Marsilio, Ilaria, Mereu, Maddalena, Contarini, Gabriella, Galuppini, Francesca, Lante, I, Filpa, V, Rugge, Massimo, Orso, Genny, Giaroni, C, Papaleo, Francesco, and Giron, MARIA CECILIA
- Published
- 2015
3. Homeoprotein OTX1 and OTX2 involvement in rat myenteric neuron adaptation after DNBS-induced colitis.
- Author
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Bistoletti M, Micheloni G, Baranzini N, Bosi A, Conti A, Filpa V, Pirrone C, Millefanti G, Moro E, Grimaldi A, Valli R, Baj A, Crema F, Giaroni C, and Porta G
- Abstract
Background: Inflammatory bowel diseases are associated with remodeling of neuronal circuitries within the enteric nervous system, occurring also at sites distant from the acute site of inflammation and underlying disturbed intestinal functions. Homeoproteins orthodenticle OTX1 and OTX2 are neuronal transcription factors participating to adaptation during inflammation and underlying tumor growth both in the central nervous system and in the periphery. In this study, we evaluated OTX1 and OTX2 expression in the rat small intestine and distal colon myenteric plexus after intrarectal dinitro-benzene sulfonic (DNBS) acid-induced colitis., Methods: OTX1 and OTX2 distribution was immunohistochemically investigated in longitudinal muscle myenteric plexus (LMMP)-whole mount preparations. mRNAs and protein levels of both OTX1 and OTX2 were evaluated by qRT-PCR and Western blotting in LMMPs., Results: DNBS-treatment induced major gross morphology and histological alterations in the distal colon, while the number of myenteric neurons was significantly reduced both in the small intestine and colon. mRNA levels of the inflammatory markers, TNFα, pro-IL1β, IL6, HIF1α and VEGFα and myeloperoxidase activity raised in both regions. In both small intestine and colon, an anti-OTX1 antibody labeled a small percentage of myenteric neurons, and prevalently enteric glial cells, as evidenced by co-staining with the glial marker S100β. OTX2 immunoreactivity was present only in myenteric neurons and was highly co-localized with neuronal nitric oxide synthase. Both in the small intestine and distal colon, the number of OTX1- and OTX2-immunoreactive myenteric neurons significantly increased after DNBS treatment. In these conditions, OTX1 immunostaining was highly superimposable with inducible nitric oxide synthase in both regions. OTX1 and OTX2 mRNA and protein levels significantly enhanced in LMMP preparations of both regions after DNBS treatment., Conclusions: These data suggest that colitis up-regulates OTX1 and OTX2 in myenteric plexus both on site and distantly from the injury, potentially participating to inflammatory-related myenteric ganglia remodeling processes involving nitrergic transmission., Competing Interests: The authors declare that they have no competing interests., (© 2020 Bistoletti et al.)
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- 2020
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4. Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice.
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Bistoletti M, Caputi V, Baranzini N, Marchesi N, Filpa V, Marsilio I, Cerantola S, Terova G, Baj A, Grimaldi A, Pascale A, Frigo G, Crema F, Giron MC, and Giaroni C
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Brain pathology, Dysbiosis chemically induced, Dysbiosis pathology, Enteric Nervous System pathology, Irritable Bowel Syndrome chemically induced, Irritable Bowel Syndrome metabolism, Irritable Bowel Syndrome pathology, Mice, Neurons metabolism, Neurons pathology, Signal Transduction drug effects, Anti-Bacterial Agents adverse effects, Brain metabolism, Brain-Derived Neurotrophic Factor biosynthesis, Dysbiosis metabolism, Enteric Nervous System metabolism, Gene Expression Regulation drug effects, Membrane Glycoproteins biosynthesis, Protein-Tyrosine Kinases biosynthesis
- Abstract
Antibiotic use during adolescence may result in dysbiosis-induced neuronal vulnerability both in the enteric nervous system (ENS) and central nervous system (CNS) contributing to the onset of chronic gastrointestinal disorders, such as irritable bowel syndrome (IBS), showing significant psychiatric comorbidity. Intestinal microbiota alterations during adolescence influence the expression of molecular factors involved in neuronal development in both the ENS and CNS. In this study, we have evaluated the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) in juvenile mice ENS and CNS, after a 2-week antibiotic (ABX) treatment. In both mucosa and mucosa-deprived whole-wall small intestine segments of ABX-treated animals, BDNF and TrKB mRNA and protein levels significantly increased. In longitudinal muscle-myenteric plexus preparations of ABX-treated mice the percentage of myenteric neurons staining for BDNF and TrkB was significantly higher than in controls. After ABX treatment, a consistent population of BDNF- and TrkB-immunoreactive neurons costained with SP and CGRP, suggesting up-regulation of BDNF signaling in both motor and sensory myenteric neurons. BDNF and TrkB protein levels were downregulated in the hippocampus and remained unchanged in the prefrontal cortex of ABX-treated animals. Immunostaining for BDNF and TrkB decreased in the hippocampus CA3 and dentate gyrus subregions, respectively, and remained unchanged in the prefrontal cortex. These data suggest that dysbiosis differentially influences the expression of BDNF-TrkB in the juvenile mice ENS and CNS. Such changes may potentially contribute later to the development of functional gut disorders, such as IBS, showing psychiatric comorbidity., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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5. Changes in hyaluronan deposition in the rat myenteric plexus after experimentally-induced colitis.
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Filpa V, Bistoletti M, Caon I, Moro E, Grimaldi A, Moretto P, Baj A, Giron MC, Karousou E, Viola M, Crema F, Frigo G, Passi A, Giaroni C, and Vigetti D
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- Animals, Benzenesulfonates, Cells, Cultured, Colitis chemically induced, Colon metabolism, Colon pathology, Disease Models, Animal, Gastrointestinal Motility, Gene Expression Regulation, Humans, Male, Mitochondrial Proteins metabolism, Protein Transport, Rats, Rats, Sprague-Dawley, Colitis metabolism, Hyaluronan Synthases metabolism, Hyaluronic Acid metabolism, Myenteric Plexus metabolism, Neurons metabolism
- Abstract
Myenteric plexus alterations hamper gastrointestinal motor function during intestinal inflammation. Hyaluronan (HA), an extracellular matrix glycosaminoglycan involved in inflammatory responses, may play a role in this process. In the colon of control rats, HA-binding protein (HABP), was detected in myenteric neuron soma, perineuronal space and ganglia surfaces. Prominent hyaluronan synthase 2 (HAS2) staining was found in myenteric neuron cytoplasm, suggesting that myenteric neurons produce HA. In the myenteric plexus of rats with 2, 4-dinitrobenzene sulfonic (DNBS)-induced colitis HABP staining was altered in the perineuronal space, while both HABP staining and HA levels increased in the muscularis propria. HAS2 immunopositive myenteric neurons and HAS2 mRNA and protein levels also increased. Overall, these observations suggest that inflammation alters HA distribution and levels in the gut neuromuscular compartment. Such changes may contribute to alterations in the myenteric plexus.
- Published
- 2017
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6. Antibiotic-induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice.
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Caputi V, Marsilio I, Filpa V, Cerantola S, Orso G, Bistoletti M, Paccagnella N, De Martin S, Montopoli M, Dall'Acqua S, Crema F, Di Gangi IM, Galuppini F, Lante I, Bogialli S, Rugge M, Debetto P, Giaroni C, and Giron MC
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- Animals, Cecum drug effects, Cecum pathology, Dysbiosis chemically induced, Dysbiosis pathology, Gastrointestinal Motility drug effects, Ileum drug effects, Ileum innervation, Ileum pathology, Ileum physiology, Male, Mice, Inbred C57BL, Muscle Contraction drug effects, Muscle, Smooth drug effects, Muscle, Smooth physiology, Myenteric Plexus drug effects, Myenteric Plexus pathology, Stomach drug effects, Stomach pathology, Synaptic Transmission drug effects, Anti-Bacterial Agents, Dysbiosis physiopathology, Gastrointestinal Microbiome
- Abstract
Background and Purpose: Gut microbiota is essential for the development of the gastrointestinal system, including the enteric nervous system (ENS). Perturbations of gut microbiota in early life have the potential to alter neurodevelopment leading to functional bowel disorders later in life. We examined the hypothesis that gut dysbiosis impairs the structural and functional integrity of the ENS, leading to gut dysmotility in juvenile mice., Experimental Approach: To induce gut dysbiosis, broad-spectrum antibiotics were administered by gavage to juvenile (3weeks old) male C57Bl/6 mice for 14 days. Bile acid composition in the intestinal lumen was analysed by liquid chromatography-mass spectrometry. Changes in intestinal motility were evaluated by stool frequency, transit of a fluorescent-labelled marker and isometric muscle responses of ileal full-thickness preparations to receptor and non-receptor-mediated stimuli. Alterations in ENS integrity were assessed by immunohistochemistry and Western blot analysis., Key Results: Antibiotic treatment altered gastrointestinal transit, luminal bile acid metabolism and bowel architecture. Gut dysbiosis resulted in distorted glial network, loss of myenteric plexus neurons, altered cholinergic, tachykininergic and nitrergic neurotransmission associated with reduced number of nNOS neurons and different ileal distribution of the toll-like receptor TLR2. Functional defects were partly reversed by activation of TLR2 signalling., Conclusions and Implications: Gut dysbiosis caused complex morpho-functional neuromuscular rearrangements, characterized by structural defects of the ENS and increased tachykininergic neurotransmission. Altogether, our findings support the beneficial role of enteric microbiota for ENS homeostasis instrumental in ensuring proper gut neuromuscular function during critical stages of development., (© 2017 The British Pharmacological Society.)
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- 2017
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7. Nitric oxide regulates homeoprotein OTX1 and OTX2 expression in the rat myenteric plexus after intestinal ischemia-reperfusion injury.
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Filpa V, Carpanese E, Marchet S, Pirrone C, Conti A, Rainero A, Moro E, Chiaravalli AM, Zucchi I, Moriondo A, Negrini D, Crema F, Frigo G, Giaroni C, and Porta G
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- Animals, Arginine analogs & derivatives, Arginine pharmacology, Gastrointestinal Transit drug effects, Gastrointestinal Transit physiology, Male, Myenteric Plexus pathology, Neurons metabolism, Nitric Oxide Synthase Type I antagonists & inhibitors, Rats, Rats, Wistar, Reperfusion Injury pathology, Intestine, Small blood supply, Myenteric Plexus metabolism, Nitric Oxide metabolism, Otx Transcription Factors metabolism, Reperfusion Injury metabolism
- Abstract
Neuronal and inducible nitric oxide synthase (nNOS and iNOS) play a protective and damaging role, respectively, on the intestinal neuromuscular function after ischemia-reperfusion (I/R) injury. To uncover the molecular pathways underlying this dichotomy we investigated their possible correlation with the orthodenticle homeobox proteins OTX1 and OTX2 in the rat small intestine myenteric plexus after in vivo I/R. Homeobox genes are fundamental for the regulation of the gut wall homeostasis both during development and in pathological conditions (inflammation, cancer). I/R injury was induced by temporary clamping the superior mesenteric artery under anesthesia, followed by 24 and 48 h of reperfusion. At 48 h after I/R intestinal transit decreased and was further reduced by N
ω -propyl-l-arginine hydrochloride (NPLA), a nNOS-selective inhibitor. By contrast this parameter was restored to control values by 1400W, an iNOS-selective inhibitor. In longitudinal muscle myenteric plexus (LMMP) preparations, iNOS, OTX1, and OTX2 mRNA and protein levels increased at 24 and 48 h after I/R. At both time periods, the number of iNOS- and OTX-immunopositive myenteric neurons increased. nNOS mRNA, protein levels, and neurons were unchanged. In LMMPs, OTX1 and OTX2 mRNA and protein upregulation was reduced by 1400W and NPLA, respectively. In myenteric ganglia, OTX1 and OTX2 staining was superimposed with that of iNOS and nNOS, respectively. Thus in myenteric ganglia iNOS- and nNOS-derived NO may promote OTX1 and OTX2 upregulation, respectively. We hypothesize that the neurodamaging and neuroprotective roles of iNOS and nNOS during I/R injury in the gut may involve corresponding activation of molecular pathways downstream of OTX1 and OTX2. NEW & NOTEWORTHY Intestinal ischemia-reperfusion (I/R) injury induces relevant alterations in myenteric neurons leading to dismotility. Nitrergic neurons seem to be selectively involved. In the present study the inference that both neuronal and inducible nitric oxide synthase (nNOS and iNOS) expressing myenteric neurons may undergo important changes sustaining derangements of motor function is reinforced. In addition, we provide data to suggest that NO produced by iNOS and nNOS regulates the expression of the vital transcription factors orthodenticle homeobox protein 1 and 2 during an I/R damage., (Copyright © 2017 the American Physiological Society.)- Published
- 2017
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8. Role of glutamatergic neurotransmission in the enteric nervous system and brain-gut axis in health and disease.
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Filpa V, Moro E, Protasoni M, Crema F, Frigo G, and Giaroni C
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- Animals, Gastroesophageal Reflux physiopathology, Gastrointestinal Tract innervation, Humans, Inflammatory Bowel Diseases physiopathology, Irritable Bowel Syndrome physiopathology, Neurons, Afferent physiology, Gastrointestinal Tract physiology, Gastrointestinal Tract physiopathology, Glutamic Acid physiology, Synaptic Transmission
- Abstract
Several studies have been carried out in the last 30 years in the attempt to clarify the possible role of glutamate as a neurotransmitter/neuromodulator in the gastrointestinal tract. Such effort has provided immunohistochemical, biomolecular and functional data suggesting that the entire glutamatergic neurotransmitter machinery is present in the complex circuitries of the enteric nervous system (ENS), which participates to the local coordination of gastrointestinal functions. Glutamate is also involved in the regulation of the brain-gut axis, a bi-directional connection pathway between the central nervous system (CNS) and the gut. The neurotransmitter contributes to convey information, via afferent fibers, from the gut to the brain, and to send appropriate signals, via efferent fibers, from the brain to control gut secretion and motility. In analogy with the CNS, an increasing number of studies suggest that dysregulation of the enteric glutamatergic neurotransmitter machinery may lead to gastrointestinal dysfunctions. On the whole, this research field has opened the possibility to find new potential targets for development of drugs for the treatment of gastrointestinal diseases. The present review analyzes the more recent literature on enteric glutamatergic neurotransmission both in physiological and pathological conditions, such as gastroesophageal reflux, gastric acid hypersecretory diseases, inflammatory bowel disease, irritable bowel syndrome and intestinal ischemia/reperfusion injury., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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9. Correction: antagonism of ionotropic glutamate receptors attenuates chemical ischemia-induced injury in rat primary cultured myenteric Ganglia.
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Carpanese E, Moretto P, Filpa V, Marchet S, Moro E, Crema F, Frigo G, and Giaroni C
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- 2015
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10. Interaction between NMDA glutamatergic and nitrergic enteric pathways during in vitro ischemia and reperfusion.
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Filpa V, Carpanese E, Marchet S, Prandoni V, Moro E, Lecchini S, Frigo G, Giaroni C, and Crema F
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- Animals, Enzyme Inhibitors pharmacology, Guinea Pigs, Ileum drug effects, Ileum metabolism, Male, Myenteric Plexus drug effects, Myenteric Plexus metabolism, Myenteric Plexus pathology, Neurons drug effects, Neurons metabolism, Neurons pathology, Nitrates metabolism, Nitric Oxide Synthase Type I antagonists & inhibitors, Nitric Oxide Synthase Type I genetics, Nitric Oxide Synthase Type II antagonists & inhibitors, Nitric Oxide Synthase Type II genetics, Nitrites metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Receptors, N-Methyl-D-Aspartate genetics, Receptors, N-Methyl-D-Aspartate metabolism, Reperfusion Injury genetics, Reperfusion Injury pathology, Glutamic Acid metabolism, Ileum innervation, N-Methylaspartate metabolism, Nitric Oxide metabolism, Reperfusion Injury metabolism
- Abstract
Nitric oxide (NO) and glutamate, via N-methyl-d-aspartate (NMDA) receptors, participate to changes in neuromuscular responses after ischemic/reperfusion (I/R) injury in the gut. In the present study we investigated the existence of a possible interplay between nitrergic and NMDA receptor pathways in the guinea pig ileum after in vitro I/R injury, resorting to functional and biomolecular approaches. In normal metabolic conditions NMDA concentration-dependently enhanced both glutamate (analyzed by high performance liquid chromatography with fluorimetric detection) and NO (spectrophotometrically quantified as NO2(-) and NO3(-)) spontaneous overflow from isolated ileal segments. Both effects were reduced by the NMDA antagonists, (-)-AP5 (10µM) and 5,7-diCl-kynurenic acid (10µM, 5,7-diCl-KYN). N(ω)-propyl-l-arginine (1µM, NPLA) and 1400W (10µM), respectively, nNOS and iNOS inhibitors, reduced NMDA-stimulated glutamate overflow. After in vitro I/R, glutamate overflow increased, and returned to control values in the presence of NPLA and 1400W. NO2(-) and NO3(-) levels transiently increased during I/R and were reduced by both (-)-AP5 and 5,7-diCl-KYN. In longitudinal muscle myenteric plexus preparations, iNOS mRNA and protein levels increased after in vitro I/R; both parameters were reduced to control values by (-)-AP5 and 5,7-diCl-KYN. Both antagonists were also able to reduce ischemia-induced enhancement of nNOS mRNA levels. Protein levels of GluN1, the ubiquitary subunit of NMDA receptors, increased after I/R and were reduced by both NPLA and 1400W. On the whole, this data suggests the existence of a cross-talk between NMDA receptor and nitrergic pathways in guinea pig ileum myenteric plexus, which may participate to neuronal rearrangements occurring during I/R., (Copyright © 2015 Elsevier B.V. All rights reserved.)
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- 2015
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11. Antagonism of ionotropic glutamate receptors attenuates chemical ischemia-induced injury in rat primary cultured myenteric ganglia.
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Carpanese E, Moretto P, Filpa V, Marchet S, Moro E, Crema F, Frigo G, and Giaroni C
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- 2-Amino-5-phosphonovalerate pharmacology, 6-Cyano-7-nitroquinoxaline-2,3-dione pharmacology, Animals, Cell Count, Cell Survival drug effects, Cells, Cultured, Excitatory Amino Acid Antagonists pharmacology, Ganglia blood supply, Ganglia cytology, Glucose metabolism, Immunohistochemistry, Ischemia chemically induced, Ischemia physiopathology, Male, Myenteric Plexus blood supply, Neurons drug effects, Rats, Reactive Oxygen Species metabolism, Receptors, AMPA antagonists & inhibitors, Receptors, AMPA metabolism, Receptors, Ionotropic Glutamate antagonists & inhibitors, Receptors, Kainic Acid antagonists & inhibitors, Receptors, Kainic Acid metabolism, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Receptors, N-Methyl-D-Aspartate metabolism, Reperfusion Injury physiopathology, Sodium Azide pharmacology, Ganglia metabolism, Myenteric Plexus metabolism, Neurons metabolism, Receptors, Ionotropic Glutamate metabolism
- Abstract
Alterations of the enteric glutamatergic transmission may underlay changes in the function of myenteric neurons following intestinal ischemia and reperfusion (I/R) contributing to impairment of gastrointestinal motility occurring in these pathological conditions. The aim of the present study was to evaluate whether glutamate receptors of the NMDA and AMPA/kainate type are involved in myenteric neuron cell damage induced by I/R. Primary cultured rat myenteric ganglia were exposed to sodium azide and glucose deprivation (in vitro chemical ischemia). After 6 days of culture, immunoreactivity for NMDA, AMPA and kainate receptors subunits, GluN(1) and GluA(1-3), GluK(1-3) respectively, was found in myenteric neurons. In myenteric cultured ganglia, in normal metabolic conditions, -AP5, an NMDA antagonist, decreased myenteric neuron number and viability, determined by calcein AM/ethidium homodimer-1 assay, and increased reactive oxygen species (ROS) levels, measured with hydroxyphenyl fluorescein. CNQX, an AMPA/kainate antagonist exerted an opposite action on the same parameters. The total number and viability of myenteric neurons significantly decreased after I/R. In these conditions, the number of neurons staining for GluN1 and GluA(1-3) subunits remained unchanged, while, the number of GluK(1-3)-immunopositive neurons increased. After I/R, -AP5 and CNQX, concentration-dependently increased myenteric neuron number and significantly increased the number of living neurons. Both -AP5 and CNQX (100-500 µM) decreased I/R-induced increase of ROS levels in myenteric ganglia. On the whole, the present data provide evidence that, under normal metabolic conditions, the enteric glutamatergic system exerts a dualistic effect on cultured myenteric ganglia, either by improving or reducing neuron survival via NMDA or AMPA/kainate receptor activation, respectively. However, blockade of both receptor pathways may exert a protective role on myenteric neurons following and I/R damage. The neuroprotective effect may depend, at least in part, on the ability of both receptors to increase intraneuronal ROS production.
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- 2014
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