Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Qesari, Marsela (2013) Neuropatia enterica in un modello murino di infezione del sistema nervoso enterico con Herpes simplex virus di tipo 1. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF (Tesi Dottorato XXV Ciclo)
3299Kb

Abstract (inglese)

Herpes simplex virus type 1 infection of murine enteric nervous system leads to gut neuropathy.

The functional gastrointestinal disorders (FGIDs) are a heterogeneous group of chronic conditions characterized by disabling symptoms and decreased patients’ quality of life (Corazziari et al., 2004; Talley et al., 2008). Among these diseases, the Irritable Bowel Syndrome (IBS) is the most relevant for the severe prognosis and the high social and economic burden (Drossman, 2006; Fichna and Storr, 2012; Quigley et al., 2012). In clinical practice, IBS is characterized by visceral hypersensitivity and altered bowel function (Larauche et al., 2012). Since the etiology is still poorly understood and no curative treatments are available, nowadays therapy for IBS is palliative and supportive but is notoriously unsatisfactory (Halland and Talley, 2012).
Although the underlying pathophysiology of FGIDs is still undefined, there are several evidences suggesting that functional or anatomical alterations of the enteric nervous system (ENS) disrupt gastrointestinal homeostasis determining FGIDs (De Giorgio and Camilleri, 2004; Furness, 2012). Infectious agents, such as neurotropic viruses, have been proposed to infect and disrupt ENS integrity either directly or indirectly eliciting harmful inflammatory responses by the innate and adaptive immune system (Chen et al., 2003; Facco et al., 2008; Selgrad et al., 2009). Among common pathogens the Herpes simplex virus type 1 (HSV-1), shows several interesting features as candidate pathogen involved in FGIDs, being highly prevalent in human populations (Knipe and Cliffe, 2008) and able to infect ENS neurons (Gesser and Koo, 1996; Brun et al., 2010). Our research group has recently established a novel animal model in rodents where a persistent HSV-1 infection in ENS leads to intestinal motor abnormalities with no macroscopic histological damage or clinical signs of disease (Brun et al., 2010).
The aim of my Ph.D. research project was to study the mechanisms responsible of the altered intestinal function secondary to HSV-1 infection of mice ENS. At 1-10 weeks after viral administration the presence of HSV-1 infection in the ENS determined time-dependent alterations of enteric neural network architecture, shown by an altered distribution and/or expression of specific neural proteins, such as HuC/D, peripherin e βIII-tubulin, and glial proteins, such as S100β and glial fibrillary acidic protein (GFAP; Qesari et al., 2011). These structural modifications in myenteric plexus were linked to changes in the equilibrium between excitatory and inhibitory neurotransmission, revealed by an increased expression of both enzymes, nitric oxide synthase (nNOS), acetylcholinetransferase (ChAT) and by a modified distribution of the vasoactive intestinal polypeptide (VIP), substance P (SP) and acetylcholinesterase (AChE).
The presence of an unbalanced inhibitory/excitatory activity was further confirmed by experiments on tissue cultures from longitudinal muscle with myenteric plexus (LMMP) and on gut contractility of ileum segments, mounted vertically in organ baths. Depolarization-evoked release of [3H]acetylcholine was significantly reduced for most of viral infection time course and in the same time neurally-mediated cholinergic responses to electric field stimulation were significantly reduced in the early and late phases of infection. All these data suggest that HSV-1 infection induces structural alterations and changes in neural excitatory activity and/or neurotransmitters release, all signs of an underlying enteric neuropathy (Qesari et al., 2011).
To study the role of innate immunity and of viral replication in the onset of HSV-1 infection-induced gut neurodysfunction, mice deficient for Toll-like receptor 2 (TLR2 KO) and ICP27-null HSV-1 (ICP27 KO), a mutant virus unable to replicate (Uprichard and Knipe, 1996), have subsequently been used. ICP27 KO administration induced anomalies in the ENS only in the early phases of infection to indicate an involvement of viral replication in the onset of enteric neuropathy only in the latest times of infection (Qesari et al., 2012). Recent studies have shown that an interaction between TLR2 and HSV-1 can trigger excessive signaling TLR2-dependent, leading to an excessive inflammation and tissue damage (Soberman et al., 2012). HSV-1 infection in the ENS of TLR2 KO mice induced only a reduction in nNOS positive neurons with no effects on myenteric plexus anatomy and intestinal contractile function.
In conclusion, this study demonstrated that HSV-1 infection of mice ENS triggers TLR2-mediated immune responses which are consequently responsible of myenteric plexus structural abnormaities and changes in ileal contractile function. My results also highlight TLR2 as an attractive therapeutic target for an effective modulation of pathogenic immune responses and possibly for the treatment of viral-associated neuropathies.

Abstract (italiano)

I disordini funzionali gastrointestinali (DFGI) comprendono un gruppo eterogeneo di malattie croniche i cui sintomi possono essere invalidanti e compromettere la qualità della vita dei pazienti che ne sono affetti (Corazziari et al., 2004; Talley et al., 2008). Tra queste, la sindrome dell'intestino irritabile (Irritable Bowel Syndrome, IBS) è considerata la più rilevante per la gravità della prognosi ed il forte impatto economico-sociale nella popolazione mondiale (Drossman, 2006; Fichna and Storr, 2012; Quigley et al., 2012). Le manifestazioni cliniche dell'IBS includono aumento della sensibilità viscerale ed alterazioni della motilità intestinale (Larauche et al., 2012). Essendo l'eziologia ancora poco conosciuta, a tutt'oggi le terapie disponibili sono per lo più palliative e poco soddisfacenti (Halland and Talley, 2012).
Sebbene la patofisiologia dei DFGI non sia ancora stata definita, numerose evidenze scientifiche suggeriscono che alterazioni permanenti o transitorie a carico del sistema nervoso enterico (SNE) possono determinare anomalie funzionali con compromissione dell'omeostasi del tratto gastrointestinale (De Giorgio and Camilleri, 2004; Furness, 2012). Agenti infettivi, come virus neurotropi, sono stati a lungo sospettati di rappresentare uno dei fattori in grado di interferire con l'integrità del SNE determinando alterazioni della rete neuronale sia direttamente che mediante una risposta immunitaria di tipo innato e/o adattativo spesso dannosa per l'ospite (Chen et al., 2003; Facco et al., 2008; Selgrad et al., 2009). L'Herpes simplex virus di tipo I (HSV-1), un virus neurotropo altamente diffuso nella popolazione (Knipe and Cliffe, 2008) e capace di infettare il SNE (Gesser and Koo, 1996; Brun et al., 2010), è stato proposto come un possibile agente eziopatologico coinvolto nell'insorgenza di DFGI. In questo contesto, il nostro gruppo di ricerca ha di recente descritto un nuovo modello sperimentale in roditori nel quale un'infezione persistente nel SNE ad opera dell'HSV-1 causa delle complesse anomalie funzionali in assenza di macroscopici danni istologici o segni di malattia (Brun et al., 2010).
Il mio progetto di dottorato ha avuto come obiettivo lo studio dei meccanismi responsabili dell'alterata funzione intestinale secondaria all'infezione del SNE murino da parte dell'HSV-1. L'infezione con HSV-1 ha determinato a 1-10 settimane dalla somministrazione del virus alterazioni tempo-dipendenti dell'architettura della rete nervosa enterica evidenziate da un'alterata distribuzione e/o espressione di specifiche proteine neuronali, quali HuC/D, periferina e βIII-tubulina, e di specifiche proteine gliali, quali S100β e proteina acidica fibrillare gliale (GFAP; Qesari et al., 2011). Tali cambiamenti strutturali a livello del plesso mienterico sono stati accompagnati da variazioni nell'equilibrio tra la neurotrasmissione eccitatoria ed inibitoria, rilevate da un aumento dell'espressione degli enzimi ossido nitrico sintetasi (nNOS), acetilcolintrasferasi (ChAT) e da cambiamenti nella distribuzione del polipetide intestinale vasoattivo (VIP), della sostanza P (SP) e dell'enzima acetilcolinesterasi (AChE).
La presenza di uno sbilanciamento dell'attività eccitatoria/inibitoria è stata ulteriormente confermata da studi su culture tissutali di cellule derivate dalla muscolatura longitudinale con annesso il plesso mienterico (LMMP) e di contrattilità su preparati di ileo, montati verticalmente in bagni per organo isolato. La liberazione di acetilcolina triziata in seguito a depolarizzazione è risultata ridotta in quasi tutti i tempi di infezione virale. In parallelo, la risposta colinergica neuronale evocata dalla stimolazione elettrica è risultata significativamente ridotta sia in una fase iniziale che tardiva dell'infezione. Tali risultati suggeriscono che il decorso dell'infezione virale ha indotto sia alterazioni strutturali che di eccitabilità neuronale e/o di rilascio di neurotrasmettitori, segni della presenza di una neuropatia a livello enterico (Qesari et al., 2011).
Allo scopo di studiare il ruolo dell'immunità innata e della replicazione virale nell'insorgenza della neurodisfunzione enterica indotta dall'infezione da HSV-1, si sono impiegati topi deficienti del gene che codifica per il recettore Toll-like 2 (TLR2 KO) ed un ceppo di HSV-1 deficiente del gene immediatamente precoce che codifica per la proteina ICP27 (ICP27 KO) essenziale per la replicazione virale (Uprichard and Knipe, 1996). L’infezione con ICP27 KO ha determinato alterazioni del SNE solamente nel primo periodo di infezione, a suggerire un coinvolgimento dei meccanismi di replicazione virale nell'insorgenza della neuropatia nelle fasi tardive dell’infezione (Qesari et al., 2012).
Studi recenti hanno evidenziato che l'interazione fra TLR2 e HSV-1 porta allo sviluppo di una risposta immunitaria innata con produzione eccessiva di citochine pro-infiammatorie e conseguente danno tissutale di natura neuroimmunitaria (Soberman et al., 2012). L'infezione del SNE con HSV-1 nei topi TLR2 KO ha prodotto solo una riduzione dei neuroni nitrergici nNOS positivi senza determinare anomalie strutturali del plesso mienterico ed alterazioni della contrattilità intestinale.
In conclusione, questa ricerca ha dimostrato che l'infezione del SNE in topi ad opera di HSV-1 determina alterazioni strutturali nel plesso mienterico e funzionali dell'attività contrattile dell'ileo che insorgono in seguito all'attivazione della risposta immunitaria mediata dai TLR2. Alla luce di questi risultati il mio lavoro di ricerca evidenzia i TLR2 come un interessante bersaglio molecolare per modulare le risposte immunitarie innescate da patogeni e possibilmente per il trattamento di neuropatie di origine virale.

Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Giron, Maria Cecilia
Dottorato (corsi e scuole):Ciclo 25 > Scuole 25 > SCIENZE FARMACOLOGICHE > FARMACOLOGIA, TOSSICOLOGIA E TERAPIA
Data di deposito della tesi:28 Gennaio 2013
Anno di Pubblicazione:28 Gennaio 2013
Parole chiave (italiano / inglese):neuropatia enterica; Herpes simplex virus di tipo 1; sistema nervoso enterico; toll-like receptor 2
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/12 Gastroenterologia
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze del Farmaco
Codice ID:5602
Depositato il:23 Ott 2013 10:00
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

Abad, C. et al. (2012). "VIP in Inflammatory Bowel Disease: State of the Art." Endocr Metab Immune Disord Drug Targets; 12(4):316-22 Cerca con Google

Abreu, MT. (2010). "Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function." Nat Rev Immunol; 10(2): 131-44 Cerca con Google

Adam, B. et al. (2007). “Mechanisms of disease: genetics of functional gastrointestinal disorders-searching the genes that matter.” Nat Clin Pract Gastroenterol Hepatol; 4(2): 102-10 Cerca con Google

Akira, S. and Takeda, K. (2004). "Functions of toll-like receptors: lessons from KO mice." C R Biol; 327(6): 581-9 Cerca con Google

Ammoury, RF. et al. (2009). “Functional gastrointestinal disorders: past and present.” World J Pediatr; 5(2): 103-12 Cerca con Google

Anitha, M. et al. (2012). "Gut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling." Gastroenterology; 143(4): 1006-16.e4 Cerca con Google

Anitha, M. et al. (2006). "Glial-derived neurotrophic factor modulates enteric neuronal survival and proliferation through neuropeptide Y." Gastroenterology; 131(4): 1164-78 Cerca con Google

Antonioli, L. et al. (2007). “Inhibition of adenosine deaminase attenuates inflammation in experimental colitis.” J Pharmacol Exp Ther; 322: 435-42 Cerca con Google

Aravalli, RN. et al. (2005). "Cutting edge: TLR2-mediated proinflammatory cytokine and chemokine production by microglial cells in response to herpes simplex virus." J Immunol; 175(7): 4189-93 Cerca con Google

Arduino, PG. and Porter, SR. (2008). “Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features.” J Oral Pathol Med; 37(2): 107-21 Cerca con Google

Aubé, AC. et al., (2006). “Changes in enteric neurone phenotype and intestinal functions in a transgenic mouse model of enteric glia disruption.” Gut; 55(5): 630-7 Cerca con Google

Barajon, I. et al. (2009). "Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia." J Histochem Cytochem; 57(11): 1013-23 Cerca con Google

Barbara, G. et al. (1997). “Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice.” Gastroenterology; 113(4): 1224-32 Cerca con Google

Barger, SW. et al. (1995). "S100 beta protects hippocampal neurons from damage induced by glucose deprivation." Brain Res; 677(1): 167-70 Cerca con Google

Barkhordari, E. et al. (2009). “Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome.” J Clin Immunol; 30(1): 74-9 Cerca con Google

Bassotti, G. et al., (2007). “Enteric glial cells and their role in gastrointestinal motor abnormalities: introducing the neuro-gliopathies.” World J Gastroenterol; 13(30): 4035-41 Cerca con Google

Beaulieu, JM. et al. (2002). "Induction of peripherin expression in subsets of brain neurons after lesion injury or cerebral ischemia." Brain Res; 946(2): 153-61 Cerca con Google

Belai, A. et al. (1997). "Neurochemical coding in the small intestine of patients with Crohn's disease." Gut; 40(6): 767-74 Cerca con Google

Benardini, N. et al. (2012). "Immunohistochemical analysis of myenteric ganglia and interstitial cells of Cajal in ulcerative colitis." J Cell Mol Med; 16(2): 318-27 Cerca con Google

Boyer, L. et al. (2005). "Myenteric plexus injury and apoptosis in experimental colitis." Auton Neurosci; 117: 41-53 Cerca con Google

Bradley, JC. et al. (1997). "Effects of inflammation on cell proliferation in the myenteric plexus of the guinea-pig ileum." Cell Tissue Res; 289(3): 455-61 Cerca con Google

Brun, P. et al. (2010). “Herpes simplex virus type 1 infection of the rat enteric nervous system evokes small-bowel neuromuscular abnormalities.” Gastroenterology; 138(5): 1790-801 Cerca con Google

Brun, P et al. (2012). “Role of Toll-Like Receptor 2 in intestinal immune response and dysfunction induced by Herpes Symplex virus type 1 infection of murine enteric nervous system.” Abstract; Digestive Disease Week: May 19-22, San Diego, U.S.A Cerca con Google

Bush, TG. et al. (1998). “Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice.” Cell; 93(2): 189-201 Cerca con Google

Cabarrocas, J. et al. (2003). “Role of enteric glial cells in inflammatory bowel disease.” Glia; 41(1): 81-93 Cerca con Google

Cairns, NJ. et al. (2003). "Molecular neuropathology of transgenic mouse models of Down syndrome." J Neural Transm Suppl; (61): 289-301 Cerca con Google

Camilleri, M. (2009). “Genetics and irritable bowel syndrome: from genomics to intermediate phenotype and pharmacogenetics.” Dig Dis Sci; 54(11): 2318-24 Cerca con Google

Cario, E. (2010). "Toll-like receptors in inflammatory bowel diseases: a decade later." Inflamm Bowel Dis; 16(9): 1583-97 Cerca con Google

Cario, E. et al. (2007). "Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function." Gastroenterology; 132(4): 1359-74 Cerca con Google

Castagliuolo, I. et al. (1997). "Increased substance P responses in dorsal root ganglia and intestinal macrophages during Clostridium difficile toxin A enteritis in rats." Proc Natl Acad Sci U S A; 94(9): 4788-93 Cerca con Google

Chen, JJ. et al. (2003). "Latent and lytic infection of isolated guinea pig enteric ganglia by varicella zoster virus." J Med Virol; 70 Suppl 1: S71-8 Cerca con Google

Cirillo, C. et al. (2011). "Proinflammatory stimuli activates human-derived enteroglial cells and induces autocrine nitric oxide production." Neurogastroenterol Motil; 23(9): e372-82 Cerca con Google

Clarke, G. et al. (2009). “Irritable bowel syndrome: towards biomarker identification.” Trends Mol Med;15:478-89 Cerca con Google

Corazziari, E. (2004). "Definition and epidemiology of functional gastrointestinal disorders." Best Pract Res Clin Gastroenterol; 18(4): 613-31. Cerca con Google

Cornet, A. et al. (2001). “Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease?” Proc Natl Acad Sci U S A; 98(23): 13306-11 Cerca con Google

Cuadrado, A. et al. (2002). "HuD binds to three AU-rich sequences in the 3'-UTR of neuroserpin mRNA and promotes the accumulation of neuroserpin mRNA and protein." Nucleic Acids Res; 30: 2202-11 Cerca con Google

De Giorgio, R. and Camilleri, M. (2004). “Human enteric neuropathies: morphology and molecular pathology.” Neurogastroentero. Motil; 16: 515-31 Cerca con Google

De Giorgio, R. et al. (2000). " Neurotrophin-3 and neurotrophin receptor immunoreactivity in peptidergic enteric neurons." Peptides; 21(9): 1421-6 Cerca con Google

De Giorgio, R. et al. (2003). "Anti-HuD-induced neuronal apoptosis underlying paraneoplastic gut dysmotility." Gastroenterology; 125: 70-9 Cerca con Google

De Giorgio, R. et al. (2004). "Inflammatory neuropathies of the enteric nervous system." Gastroenterology; 126(7): 1872-83 Cerca con Google

Delgado, M. and Ganea, D. (2003). "Vasoactive intestinal peptide prevents activated microglia-induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma." FASEB J; 17(13): 1922-4 Cerca con Google

Dijkstra, G. et al. (2004). "Targeting nitric oxide in the gastrointestinal tract." Curr Opin Investig Drugs; 5(5): 529-36 Cerca con Google

Donato, R. (2001). "S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles." Int J Biochem Cell Biol; 33(7): 637-68 Cerca con Google

Donato, R. et al. (2009). "S100B's double life: intracellular regulator and extracellular signal." Biochim Biophys Acta; 1793(6): 1008-22 Cerca con Google

Drossman, DA. (2006). "The functional gastrointestinal disorders and the Rome III Process." Gastroenterology; 130: 1377-1390 Cerca con Google

Efstathiou, S. and Preston, CM. (2005). “Towards an understanding of the molecular basis of herpes simplex virus latency.” Virus Res; 111(2): 108-19 Cerca con Google

Ekblad, E. and Bauer, AJ. (2004). "Role of vasoactive intestinal peptide and inflammatory mediators in enteric neuronal plasticity." Neurogastroenterol Motil; 16 Suppl 1: 123-8 Cerca con Google

Elder, GA. et al. (1999). "Age-related atrophy of motor axons in mice deficient in the mid-sized neurofilament subunit." J Cell Biol; 146: 181-92 Cerca con Google

Eng, LF. et al. (2000). "Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000)." Neurochem Res; 25(9-10): 1439-51 Cerca con Google

Esposito, G. et al. (2007). "Enteric glial-derived S100B protein stimulates nitric oxide production in celiac disease." Gastroenterology; 133: 918-25 Cerca con Google

Facco, M. et al. (2008). “T cells in the myenteric plexus of achalasia patients show a skewed TCR repertoire and react to HSV-1 antigens.” Am J Gastroenterol; 103(7): 1598-609 Cerca con Google

Fanarraga, ML. et al. (1999). "Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation." Eur J Neurosci; 11(2): 517-27 Cerca con Google

Feng, B. et al. (2012). “Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Neural and neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome.” Am J Physiol Gastrointest Liver Physiol; 302(10): G1085-98 Cerca con Google

Fernandez-Cabezudo, MJ. et al. (2010). " Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium." Immunology; 130(3): 388-98 Cerca con Google

Fichna, J. and Storr, MA. (2012). “Brain-Gut Interactions in IBS.” Front Pharmacol; 3: 127 Cerca con Google

Fournier, AE. and McKerracher, L. (1997). "Expression of specific tubulin isotypes increases during regeneration of injured CNS neurons, but not after the application of brain-derived neurotrophic factor (BDNF)." J Neurosci; 17(12): 4623-32 Cerca con Google

Furness, JB. (2012). “The enteric nervous system and neurogastroenterology.” Nat Rev Gastroenterol Hepatol; 9(5): 286-94 Cerca con Google

Furness, JB. et al. (1995). "Plurichemical transmission and chemical coding of neurons in the digestive tract." Gastroenterology; 108(2): 554-63 Cerca con Google

Furness, JB. et al. (1998). “Intrinsic primary afferent neurons of the intestine.” Prog Neurobiol; 54(1): 1-18 Cerca con Google

Furness, JB. et al. (2004). “Intrinsic primary afferent neurons and nerve circuits within the intestine.” Prog. Neurobiol; 72: 143–164 Cerca con Google

Galeazzi, F. et al. (2000). "Inflammation-induced impairment of enteric nerve function in nematode-infected mice is macrophage dependent." Am J Physiol Gastrointest Liver Physiol; 278(2): G259-65 Cerca con Google

Garthwaite, J. (2010). "New insight into the functioning of nitric oxide-receptive guanylyl cyclase: physiological and pharmacological implications." Mol Cell Biochem; 334(1-2): 221-32 Cerca con Google

Giaroni, C. et al. (1999). "Plasticity in the enteric nervous system." Gastroenterology; 117(6): 1438-58 Cerca con Google

Gies, U. et al. (2001). " Cortical cholinergic decline parallels the progression of Borna virus encephalitis." Neuroreport; 12(17): 3767-72 Cerca con Google

Giordano, C. et al. (2008). "Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion." Am J Pathol; 173(4): 1120-8 Cerca con Google

Goya,l RC. and Hirano, I. (1996). “Enteric nervous system.” N Engl J Med; 334(17): 1106-15 Cerca con Google

Gross, K. J. and Pothoulakis, C. (2007). "Role of neuropeptides in infiammatory bowel disease." Inflamm Bowel Dis; 13(7): 918-32 Cerca con Google

Halland, M. and Talley, NJ. (2012). "New treatments for IBS." Nat Rev Gastroenterol Hepatol; 10(1): 13-23 Cerca con Google

Hanevik, K. et al. (2009). “Development of functional gastrointestinal disorders after Giardia lamblia infection.” BMC Gastroenterol; 9: 27 Cerca con Google

Hardwicke, MA. and Sandri-Goldin, RM. (1994). “The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection.” J Virol; 68(8): 4797-810 Cerca con Google

Harrington, AM. et al. (2010). "Cholinergic neurotransmission and muscarinic receptors in the enteric nervous system." Prog Histochem Cytochem; 44(4): 173-202 Cerca con Google

Helfand, BT. et al. (2003). "A role for intermediate filaments in determining and maintaining the shape of nerve cells." Mol Biol Cell; 14: 5069-81 Cerca con Google

Ho, WZ. et al. (1997). "Human monocytes and macrophages express substance P and neurokinin-1 receptor." J Immunol; 159(11): 5654-60 Cerca con Google

Holzer, P. (2006). "Efferent-like roles of afferent neurons in the gut: Blood flow regulation and tissue protection." Auton Neurosci; 125(1-2): 70-5 Cerca con Google

Holzer, P. (2007). "Role of visceral afferent neurons in mucosal inflammation and defense." Curr Opin Pharmacol; 7(6): 563-9 Cerca con Google

Huttunen, HJ. et al. (2000). "Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation." J Biol Chem; 275(51): 40096-105 Cerca con Google

Ippolito, C. et al. (2009). "Quantitative evaluation of myenteric ganglion cells in normal human left colon: implications for histopathological analysis." Cell Tissue Res; 336: 191-201 Cerca con Google

Iwasaki, Y. et al. (1997). "S100 beta prevents the death of motor neurons in newborn rats after sciatic nerve section." J Neurol Sci; 151(1): 7-12 Cerca con Google

Jiang, YQ. and Oblinger, MM. (1992). "Differential regulation of beta III and other tubulin genes during peripheral and central neuron development." J Cell Sci; 103 ( Pt 3): 643-51 Cerca con Google

Johnson, G. et al. (1995). "Acetylcholinesterase of human intestinal tissue affected by Hirschsprung's disease: effect of magnesium chloride on isoforms." Clin Chim Acta; 243(2): 115-28 Cerca con Google

Jones, MP. et al. (2007). “Functional gastrointestinal disorders: an update for the psychiatrist.” Psychosomatics; 48: 93-102 Cerca con Google

Karagiannides, I. et al. (2006). "Induction of colitis causes inflammatory responses in fat depots: evidence for substance P pathways in human mesenteric preadipocytes." Proc Natl Acad Sci U S A; 103(13): 5207-12 Cerca con Google

Kawai, T. and Akira, S. (2010). "The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors." Nat Immunol; 11(5): 373-84 Cerca con Google

Kawashima, K. et al. (2007). "Expression and function of genes encoding cholinergic components in murine immune cells." Life Sci; 80(24-25): 2314-9 Cerca con Google

Khan, I. and Collins, SM. (1994). "Expression of cytokines in the longitudinal muscle myenteric plexus of the inflamed intestine of rat." Gastroenterology; 107(3): 691-700 Cerca con Google

Knipe, DM. and Cliffe, A. (2008). “Chromatin control of herpes simplex virus lytic and latent infection.” Nat Rev Microbiol; 6(3): 211-21 Cerca con Google

Kotsakis, A. et al. (2001). "Microtubule reorganization during herpes simplex virus type 1 infection facilitates the nuclear localization of VP22, a major virion tegument protein." J Virol; 75(18): 8697-711 Cerca con Google

Kramer, MF. et al. (2003). "Latent herpes simplex virus infection of sensory neurons alters neuronal gene expression." J Virol; 77: 9533-41 Cerca con Google

Kraneveld, AD. et al. (2008). "Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome: future therapeutic targets." Eur J Pharmacol; 585(2-3): 361-74 Cerca con Google

Kriz, J. et al. (2000). "Electrophysiological properties of axons in mice lacking neurofilament subunit genes: disparity between conduction velocity and axon diameter in absence of NF-H." Brain Res; 885: 32-44 Cerca con Google

Kurt-Jones, EA. et al. (2004). "Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis." Proc Natl Acad Sci U S A; 101(5): 1315-20 Cerca con Google

Kurt-Jones, EA. et al. (2005). "The role of toll-like receptors in herpes simplex infection in neonates." J Infect Dis; 191(5): 746-8 Cerca con Google

Lai, JP. et al. (1998). "Human lymphocytes express substance P and its receptor." J Neuroimmunol; 86(1): 80-6 Cerca con Google

Larauche, M. et al. (2012). “Stress and visceral pain: from animal models to clinical therapies.” Exp Neurol; 233(1): 49-67 Cerca con Google

Lariviere, RC. and Julien, JP. (2004). "Functions of intermediate filaments in neuronal development and disease." J Neurobiol; 58(1): 131-48 Cerca con Google

Lee, WC. et al. (2012). "A neuronal death model: overexpression of neuronal intermediate filament protein peripherin in PC12 cells." J Biomed Sci; 19:8 Cerca con Google

Lieb, K. et al. (1997). "The neuropeptide substance P activates transcription factor NF-kappa B and kappa B-dependent gene expression in human astrocytoma cells." J Immunol;159(10): 4952-8 Cerca con Google

Liem, RK. and Messing, A. (2009). "Dysfunctions of neuronal and glial intermediate filaments in disease." J Clin Invest; 119(7): 1814-24 Cerca con Google

Lima, GK. et al. (2010). "Toll-like receptor (TLR) 2 and TLR9 expressed in trigeminal ganglia are critical to viral control during herpes simplex virus 1 infection." Am J Pathol; 177(5): 2433-45 Cerca con Google

Lomax, AE. et al. (2005). " Plasticity of the enteric nervous system during intestinal inflammation." Neurogastroenterol Motil; 17(1): 4-15 Cerca con Google

Luna, C. et al. (2002). " Characterization of four Toll related genes during development and immune responses in Anopheles gambiae." Insect Biochem Mol Biol; 32(9): 1171-9 Cerca con Google

Mayer, EA. and Collins, SM. (2002). “Evolving pathophysiologic models of functional gastrointestinal disorders.” Gastroenterology; 122(7): 2032-48 Cerca con Google

Mayer, EA. et al. (2008). “Functional GI disorders: from animal models to drug development.” Gut; 57(3): 384-404 Cerca con Google

McCann, SM. et al. (2000). " The mechanism of action of cytokines to control the release of hypothalamic and pituitary hormones in infection." Acad Sci; 917: 4-18 Cerca con Google

McCarthy, AM. et al. (1989). “Herpes simplex virus type 1 ICP27 deletion mutants exhibit altered patterns of transcription and are DNA deficient.” J Virol; 63(1): 18-27 Cerca con Google

McLean, J. et al. (2010). "Distinct biochemical signatures characterize peripherin isoform expression in both traumatic neuronal injury and motor neuron disease." J Neurochem; 114(4): 1177-92 Cerca con Google

Middeldorp, J. and Hol, EM. (2011). "GFAP in health and disease." Prog Neurobiol; 93(3): 421-43 Cerca con Google

Morrison, LA, (2004). "The Toll of herpes simplex virus infection." Trends Microbiol; 12(8): 353-6 Cerca con Google

Murphy, EM. et al. (2007). "Quantification of subclasses of human colonic myenteric neurons by immunoreactivity to Hu, choline acetytransferase and nitric oxide synthase." Neurogastroenterol Motil; 19: 126-134 Cerca con Google

Natale, G. et al. (2008). "Parkinson's disease and the gut: a well known clinical association in need of an effective cure and explanation." Neurogastroenterol Motil; 20(7): 741-9 Cerca con Google

Neunlist, M. et al. (2007). “Enteric glia inhibit intestinal epithelial cell proliferation partly through a TGF-beta1-dependent pathway.” Am J Physiol Gastrointest Liver Physiol; 292(1): G231-41 Cerca con Google

Okano, HJ. and Darnell, RB. (1997). " A hierarchy of Hu RNA binding proteins in developing and adult neurons." J Neurosci; 17(9): 3024-37 Cerca con Google

Okun, E. et al. (2009). "Toll-like receptors in neurodegeneration." Brain Res Rev; 59(2): 278-92. Cerca con Google

Olson, JK. and Miller, SD. (2004). "Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs." J Immunol; 173(6): 3916-24 Cerca con Google

Omary, MB. (2009). "IF-pathies": a broad spectrum of intermediate filament-associated diseases." J Clin Invest; 119(7): 1756-62 Cerca con Google

Perng, GC. and Jones, C. (2010). “Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle.” Interdiscip Perspect Infect Dis; 2010: 262415 Cerca con Google

Perng, GC. et al. (2000). “Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript.” Science; 287(5457): 1500-3 Cerca con Google

Perrone-Bizzozero, N. and Bolognani, F. (2002). "Role of HuD and other RNA-binding proteins in neural development and plasticity." J Neurosci Res; 68: 121-6 Cerca con Google

Phillips, RJ. et al. (2004). "Loss of glia and neurons in the myenteric plexus of the aged Fischer 344 rat." Anat Embryol; 209: 19-30 Cerca con Google

Poli, E. et al. (2001). "Morphological and functional alterations of the myenteric plexus in rats with TNBS-induced colitis." Neurochem Res; 26: 1085-93 Cerca con Google

Qesari, M. et al. (2012). “Severity of enteric nervous system neuropathy during Herpes simplex virus type 1 infection is related to viral replication” Oral comunication; 6th European Congress of Pharmacology: July 17-20, Granada, Spain Cerca con Google

Qesari, M. et al. (2011). "Neuropatia enterica in un modello murino di infezione del sistema nervoso enterico con herpes simplex virus di tipo 1." Abstract; XIV Congresso Nazionale GISMAD: 18-19 Marzo, Mestre, Italia Cerca con Google

Qesari, M. et al. (2011). " Herpes Simplex virus type-1 infection of the enteric nervous system leads to gut neuroanatomical and neurochemical abnormalities." Abstract; 35° Congresso Nazionale della SIF: 14-17 Settembre, Bologna, Italia Cerca con Google

Qin, HY. et al. (2012). “Key factors in developing the trinitrobenzene sulfonic acid-induced post-inflammatory irritable bowel syndrome model in rats.” World J Gastroenterol; 18(20): 2481-92 Cerca con Google

Quigley, EM. (1999). “Disturbances in small bowel motility.” Baillieres Best Pract Res Clin Gastroenterol; 13: 385-95 Cerca con Google

Quigley, EM. et al. (2012).” A global perspective on irritable bowel syndrome: a consensus statement of the World Gastroenterology Organisation Summit Task Force on irritable bowel syndrome.” J Clin Gastroenterol; 46(5): 356-66 Cerca con Google

Rakoff-Nahoum, S. et al. (2004). "Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis." Cell; 118(2): 229-41 Cerca con Google

Rakoff-Nahoum, S. et al. (2006). "Role of toll-like receptors in spontaneous commensal-dependent colitis." Immunity; 25(2): 319-29 Cerca con Google

Reske, A. et al. (2007). “Understanding HSV-1 entry glycoproteins.” Rev Med Virol; 17(3): 205-15 Cerca con Google

Ringheim, GE. and Conant, K. (2004). "Neurodegenerative disease and the neuroimmune axis (Alzheimer's and Parkinson's disease, and viral infections)." J Neuroimmunol; 147(1-2): 43-9 Cerca con Google

Rivera, RL. (2011). "The involvement of nitric oxide synthase neurons in enteric neuropathies." Neurogastroenterol Motil; 23(11): 980-8 Cerca con Google

Robertson, J. et al. (2001). "Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinfiammatory cytokine tumor necrosis factor-α." Journal of Cell Biology; 155: 217-226 Cerca con Google

Rodrigues, D. M. et al. (2011). "Glial cell line-derived neurotrophic factor is a key neurotrophin in the postnatal enteric nervous system." Neurogastroenterol Motil; 23(2): e44-56 Cerca con Google

Roizman, B. and Knipe, DM. (2007). “Herpes simplex viruses” p. 2501-2602. In Knipe, DM., Howley, PM., Griffin, DE., Lamb, RA., Martin, MA., Roizman, B. and Straus, SE. Fields virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA Cerca con Google

Rolls, A. et al. (2007). "Toll-like receptors modulate adult hippocampal neurogenesis." Nat Cell Biol; 9(9): 1081-8 Cerca con Google

Rühl, A. et al. (2001). “Isolation of enteric glia and establishment of transformed enteroglial cell lines from the myenteric plexus of adult rat.” Neurogastroenterol Motil; 13(1): 95-106 Cerca con Google

Rühl, A. et al. (2004). “Enteric glia.” Neurogastroenterol Motil; 16 Suppl 1: 44-9 Cerca con Google

Saeed, RW. et al. (2005). "Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation." J Exp Med; 201(7): 1113-23 Cerca con Google

Saffrey, MJ. and Burnstock, G. (1994). "Growth factors and the development and plasticity of the enteric nervous system." J Auton Nerv Syst; 49(3): 183-96 Cerca con Google

Samaniego, LA. et al. (1995). “Functional interactions between herpes simplex virus immediate-early proteins during infection: gene expression as a consequence of ICP27 and different domains of ICP4.” J Virol; 69(9): 5705-15 Cerca con Google

Sandgren, K et al. (2003). "Vasoactive intestinal peptide and nitric oxide promote survival of adult rat myenteric neurons in culture." J Neurosci Res; 72(5): 595-602 Cerca con Google

Sandri-Goldin, RM. (2008). “The many roles of the regulatory protein ICP27 during herpes simplex virus infection.” Front Biosci; 13: 5241-56 Cerca con Google

Sanovic, S. et al. (1999). "Damage to the enteric nervous system in experimental colitis." Am J Pathol; 155: 1051-7 Cerca con Google

Selgrad, M. et al. (2009). “JC virus infects the enteric glia of patients with chronic idiopathic intestinal pseudo-obstruction.” Gut; 58: 25-32 Cerca con Google

Shah, RN. et al. (2004). "Achalasia presenting after operative and nonoperative trauma." Dig Dis Sci; 49(11-12): 1818-21 Cerca con Google

Sharkey, KA. and Kroese, AB. (2001). "Consequences of intestinal inflammation on the enteric nervous system: neuronal activation induced by inflammatory mediators." Anat Rec; 262(1): 79-90 Cerca con Google

Sloane, JA. et al. (2010). "Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2." Proc Natl Acad Sci U S A; 107(25): 11555-60 Cerca con Google

Soberman, RJ. Et al. (2012). “CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2. PLoS One; 7(10): e47740 Cerca con Google

Sofroniew, MV. (2005). "Reactive astrocytes in neural repair and protection." Neuroscientist; 11(5): 400-7 Cerca con Google

Takeda, K. and Akira, S. (2004). "Microbial recognition by Toll-like receptors." J Dermatol Sci; 34(2): 73-82 Cerca con Google

Takeda, K. and Akira, S. (2005). "Toll-like receptors in innate immunity." Int Immunol; 17(1): 1-14 Cerca con Google

Talley, NJ. (2008). “Functional gastrointestinal disorders as a public health problem.” Neurogastroenterol Motil; 20 Suppl 1: 121-9 Cerca con Google

Terhorst, D. et al. (2007). "Monocyte-derived dendritic cells from highly atopic individuals are not impaired in their pro-inflammatory response to toll-like receptor ligands." Clin Exp Allergy; 37(3): 381-90 Cerca con Google

Texereau, J. et al. (2005). "The importance of Toll-like receptor 2 polymorphisms in severe infections." Clin Infect Dis; 41 Suppl 7: S408-15 Cerca con Google

Thoenen, H. (2000). "Neurotrophins and activity-dependent plasticity." Prog Brain Res; 128: 183-91 Cerca con Google

Tjong, YW. et al. (2011). "Role of neuronal nitric oxide synthase in colonic distension-induced hyperalgesia in distal colon of neonatal maternal separated male rats." Neurogastroenterol Motil; 23(7): 666-e278 Cerca con Google

Törnblom, H. et al. (2002). “Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome.” Gastroenterolog.; 123: 1972-9 Cerca con Google

Törnblom, H. et al. (2007). “Autoantibodies in patients with gut motility disorders and enteric neuropathy.” Scand J Gastroenterol; 42: 1289-93 Cerca con Google

Turer, EE. et al. (2008). "Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20." J Exp Med; 205(2): 451-64 Cerca con Google

Uprichard, SL. and Knipe, DM. (1996). "Herpes simplex ICP27 mutant viruses exhibit reduced expression of specific DNA replication genes." J Virol; 70(3): 1969-80 Cerca con Google

Vasina, V. et al. (2006). "Enteric neuroplasticity evoked by inflammation." Auton Neurosci; 126-127: 264-72 Cerca con Google

Vincent, AM. et al. (2007). "Receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress." Endocrinology; 148(2): 548-58 Cerca con Google

Voltz, RD. et al. (1997). "Paraneoplastic encephalomyelitis: an update of the effects of the anti-Hu immune response on the nervous system and tumour." J Neurol Neurosurg Psychiatry; 63(2): 133-6 Cerca con Google

von Boyen, GB. et al. (2004). “Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia.” Gut; 53(2): 222-8 Cerca con Google

von Boyen, GB. et al. (2001). "Enteric nervous plasticity and development: dependence on neurotrophic factors." J Gastroenterol; 37(8): 583-8 Cerca con Google

Wang, H. et al. (2003). "Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation." Nature; 421(6921): 384-8 Cerca con Google

Wang, JP. et al. (2012). "Role of specific innate immune responses in herpes simplex virus infection of the central nervous system." J Virol; 86(4): 2273-81 Cerca con Google

Weir, JP. (2001). “Regulation of herpes simplex virus gene expression.” Gene; 271(2): 117-30 Cerca con Google

Zambrano, A. et al. (2008). "Neuronal cytoskeletal dynamic modification and neurodegeneration induced by infection with herpes simplex virus type 1." J Alzheimers Dis; 14(3): 259-69 Cerca con Google

Zhao, D. et al. (2002). "Substance P-stimulated interleukin-8 expression in human colonic epithelial cells involves Rho family small GTPases." Biochem J; 368(Pt 2): 665-72 Cerca con Google

Zhou, L. and Zhu, DY. (2009). "Neuronal nitric oxide synthase: structure, subcellular localization, regulation, and clinical implications." Nitric Oxide; 20(4): 223-30 Cerca con Google

Zoppellaro, C. (2010). "Infezione da Herpes simplex virus-1 nel sistema nervoso enterico: un innovativo modello di alterazione della motilità intestinale." Tesi di Dottorato della Scuola di Dottorato di Ricerca in Scienze Farmaceutiche, Università degli Studi di Padova Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record