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Negro, Samuele (2016) Signaling and transcriptomics at the degenerating-regenerating neuromuscular junction. [Tesi di dottorato]

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Abstract (inglese)

The neuromuscular junction (NMJ) is a specialized tripartite synapse that allows the transmission of an electrical impulse travelling along the axon to the muscle. It is composed of the motor axon terminal (MAT), covered by perisynaptic Schwann cells (PSCs), and the muscle fibre (MF), which are separated by a basal lamina. The NMJ is not protected by anatomical barriers: it can be therefore exposed to traumas, to the attack of many pathogens including neurotoxins, and affected by many neuromuscular diseases such as amyotrophic lateral sclerosis and immune-mediated disorders, such as the Guillain-Barré and Miller Fisher syndromes. For these reasons and for its essential role in life and survival the NMJ has retained throughout vertebrate evolution an intrinsic ability for repair and regeneration, differently from central synapses. After nerve injury the glial cells of the NMJ, the PSCs, acquire a regenerative phenotype and release a series of factors that act on the stump of the MAT, providing several cues to promote neuronal regeneration. Following peripheral nerve injury, many changes taking place at the NMJ have been reported so far, but the inter- and intra-cellular signaling that occur during MAT degeneration and, more importantly, those governing the ensuing regeneration are not completely understood.
We have recently established a model to study NMJ degeneration and regeneration in mice based on the specific action of -latrotoxin, a presynaptic neurotoxin isolated from the venom of the black widow spider, which targets specifically the presynaptic terminal causing its complete degeneration. Following intoxication and the subsequent clearing of MAT debris by PSCs, the axon stump regrows in few days in mice allowing complete NMJ recovery. This toxin represents therefore a simple and controlled method to induce an acute, localized and reversible nerve terminal degeneration not blurred by inflammation, and can help to identify molecules involved in the intra- and inter-cellular signalling governing NMJ regeneration.
In the search of candidate molecules involved in triggering and sustaining nerve recovery we choose to perform a transcriptomic analysis of the mouse NMJs at different time points after injection of -latrotoxin. This approach has been very challenging: to our knowledge a transcriptomic analysis of the sole NMJ was never reported before. We succeeded in collecting a number of NMJs suitable for RNA isolation and sequencing of both coding and non–coding RNAs. Among the coding transcripts we selected a series of messenger RNAs (mRNAs) that are expressed at low level in controls, at higher levels during regeneration, and then return to basal when substantial regeneration is attained and we selected the mRNA encoding for the chemokine CXCL12. We found that CXCL12 is produced by PSCs during nerve degeneration, and that intraperitoneal injection of a neutralizing antibody for CXCL12 slows down the regeneration process. Moreover, the exposure of primary motor neurons to the recombinant chemokine stimulates neurite growth.
These data suggest that CXCL12 is an important factor released by PSCs with a crucial role in the nerve terminal regeneration process.
Parallely, we looked for molecules released by injured neurons that could activate SCs and stimulate nerve regeneration. We found that ATP released by intoxicated neurons activates a series of intracellullar signaling pathways in SCs including Ca2+, adenylate cyclase, ERK 1/2 and CREB, that are of fundamental importance for the recovery of nerve function. We propose ATP as an important alarm signal partecipating in the cross-talk between degenerating nerve terminals and adjacent PSCs not only in a model of degeneration by a spider toxin, but also in different forms of neurodegeneration of the presynaptic nerve terminal.

Abstract (italiano)

La giunzione neuromuscolare è una regione anatomica altamente specializzata in cui i segnali elettrici che corrono lungo l’assone del motoneurone sono convertiti in segnali chimici, che vengono a loro volta riconosciuti dalle cellule muscolari causandone la contrazione. E’ composta dal terminale assonico del motoneurone, dalle cellule di Schwann perisinaptiche che avvolgono quest’ultimo, dalla fibra muscolare e dalla lamina basale. La giunzione neuromuscolare non è protetta da barriere anatomiche e pertanto può essere bersaglio di differenti patogeni come virus, batteri, tossine. Inoltre la giunzione può essere affetta da diverse patologie quali la sclerosi laterale amiotrofica o la Sindrome di Guillain-Barrè di origine autoimmune. Per questi motivi e per la sua funzione fisiologica essenziale per la vita degli animali, non sorprende dunque la capacità della giunzione neuromuscolare di rigenerare e recuperare la sua funzionalità a seguito di differenti tipi di danno. Questa abilità si è mantenuta durante l’evoluzione animale, e differenzia le sinapsi del sistema nervoso periferico da quelle del centrale, che non hanno invece capacità rigenerativa.
In seguito a denervazione le cellule di Schwann perisinaptiche mostrano una grande plasticità, de-differenziando ed iniziando a proliferare. Esse partecipano attivamente ai processi di rigenerazione nervosa, contribuendo al rilascio di diversi fattori in grado di agire sul terminale nervoso degenerato promuovendone la ricrescita ed il pieno recupero della sua funzionalità. Sono ancora poco conosciuti gli eventi intra- ed inter-cellulari che avvengono alla giunzione durante la degenerazione e soprattutto quelli che governano il processo rigenerativo del terminale nervoso.
A tale scopo, nel nostro laboratorio è stato messo a punto un approccio sperimentale innovativo che permette di studiare la degenerazione e rigenerazione della giunzione neuromuscolare sfruttando il meccanismo d’azione di una neurotossina presinaptica animale, α-Latrotoxin, presente nel veleno dei ragni del genere Latrodectus. Questa tossina agisce selettivamente a livello della membrana presinaptica del motoneurone, inducendo un danno acuto e localizzato del terminale nervoso. Il terminale degenera rapidamente ma in breve tempo, in seguito alla rimozione dei detriti neuronali da parte delle cellule di Schwann, è in grado di ricrescere e di riacquisire una piena funzionalità.
L’azione di tali neurotossine rappresenta quindi un sistema appropriato e controllato per indurre una degenerazione acuta, localizzata e reversibile del terminale nervoso, evitando il coinvolgimento di molti tipi cellulari e mediatori dell’infiammazione come accade nel corso della degenerazione indotta da cut/crush del nervo sciatico, tradizionalmente utilizzato fino ad oggi. Questo approccio può dunque aiutare a definire i meccanismi molecolari ed identificare i segnali intra- ed inter-cellulari alla base della degenerazione e rigenerazione nervosa.
Con lo scopo di identificare molecole in grado di promuovere la rigenerazione del terminale nervoso, abbiamo messo a punto un protocollo che ci ha permesso di ottenere per la prima volta un’analisi trascrizionale a livello di giunzione neuromuscolare durante le diverse fasi di degenerazione e rigenerazione del terminale nervoso periferico in seguito ad intossicazione con α-latrotoxin. Abbiamo isolato e sequenziato da un numero adeguato di giunzioni RNA codificanti e non. Tra i diversi trascritti abbiamo selezionato quelli che presentavano un basso valore di espressione nel controllo, un aumento durante le fase rigenerativa per poi tornare ad un livello basale quando la rigenerazione è conclusa. Tra questi abbiamo approfondito lo studio della chemochina CXCL12, dimostrando che viene prodotta dalle cellule di Schwann terminali durante la degenerazione nervosa, e che l’iniezione intraperitoneale di un anticorpo neutralizzante comporta un ritardo nel processo rigenerativo. Inoltre abbiamo dimostrato che questa chemochina è in grado di promuovere la crescita dei neuriti di motoneuroni in coltura. Questi risultati suggeriscono come CXCL12 sia un importante fattore rilasciato dalle cellule di Schwann perisinaptiche con un ruolo cruciale nei processi rigenerativi del terminale nervoso.
Parallelamente abbiamo indagato quali potessero essere i segnali di allarme rilasciati dal terminale nervoso in degenerazione in grado di attivare le cellule di Schwann e di promuovere la rigenerazione nervosa. Abbiamo dimostrato che l’ATP viene rilasciato da neuroni in seguito ad intossicazione con α-latrotoxin, ed è in grado di attivare nelle cellule di Schwann diverse vie di segnalazione intracellulari quali il calcio, l’AMP ciclico, ERK1/2, CREB, importanti per il recupero della funzionalità nervosa in seguito a danno.
I dati presentati in questa tesi identificano l’ATP come importante molecola segnale nella comunicazione tra il terminale nervoso in degenerazione e le vicine cellule di Schwann perisinaptiche, ed estendono tale ruolo anche ad altre forme di degenerazione del terminale nervoso presinaptico.

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Tipo di EPrint:Tesi di dottorato
Relatore:Rossetto, Ornella
Dottorato (corsi e scuole):Ciclo 28 > Scuole 28 > BIOSCIENZE E BIOTECNOLOGIE > NEUROBIOLOGIA
Data di deposito della tesi:29 Gennaio 2016
Anno di Pubblicazione:29 Gennaio 2016
Parole chiave (italiano / inglese):neuromuscular junction/nerve regeneration/neurotoxin/signaling/transcriptomic
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/04 Patologia generale
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:9389
Depositato il:20 Ott 2016 12:14
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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.

Angaut-Petit D, Molgo J, Connold AL, Faille L. The levator auris longus muscle of the mouse: a convenient preparation for studies of short- and long-term presynaptic effects of drugs or toxins. Neurosci Lett. (1987) Cerca con Google

Ansselin AD, Davey DF, Allen DG. Extracellular ATP increases intracellular calcium in cultured adult Schwann cells. Neuroscience. (1997) Cerca con Google

Arakawa Y, Bito H, Furuyashiki T, Tsuji T, Takemoto-Kimura S, Kimura K, Nozaki K, Hashimoto N, Narumiya S. Control of axon elongation via an SDF-1alpha/Rho/mDia pathway in cultured cerebellar granule neurons. J Cell Biol. (2003) Cerca con Google

Arce V, Garces A, de Bovis B, Filippi P, Henderson C, Pettmann B, deLapeyrière O. Cardiotrophin-1 requires LIFRbeta to promote survival of mouse motoneurons purified by a novel technique. J Neurosci Res (1999). Cerca con Google

Arthur-Farraj, P. J. et al. c Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron. (2012). Cerca con Google

Ashton AC, Volynski KE, Lelianova VG, Orlova EV, Van Renterghem C, Canepari M, Seagar M, Ushkaryov YA. alpha-Latrotoxin, acting via two Ca2+-dependent pathways, triggers exocytosis of two pools of synaptic vesicles. J Biol Chem.(2001) Cerca con Google

Auld DS, Robitaille R. Perisynaptic Schwann cells at the neuromuscular junction: nerve- and activity-dependent contributions to synaptic efficacy, plasticity, and reinnervation. Neuroscientist. (2003) Cerca con Google

Baxter RL, Vega-Riveroll LJ, Deuchars J, Parson SH A2A adenosine receptors are located on presynaptic motor nerve terminals in the mouse. Synapse. (2005) Cerca con Google

Ben-Yaakov Keren, Shachar Y Dagan, Yael Segal-Ruder, Ophir Shalem, Deepika Vuppalanchi, Dianna E Willis, Dmitry Yudin, Ida Rishal, Franziska Rother, Michael Bader, Armin Blesch, Yitzhak Pilpel, Jeffery L Twiss, and Mike Fainzilber. Axonal transcription factors signal retrogradely in lesioned peripheral nerve. EMBO J. (2012) Cerca con Google

Beirowski B, Adalbert R, Wagner D, Grumme DS, Addicks K, Ribchester RR, Coleman MP. Cerca con Google

The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves. BMC Neurosci. (2005) Cerca con Google

Bishop, D.L., T. Misgeld, M.K. Walsh, W.B. Gan, J.W. Lichtman Axon branch removal at developing synapses by axosome shedding. Neuron. .( 2004) Cerca con Google

Bourque MJ, Robitaille R. Endogenous peptidergic modulation of perisynaptic Schwann cells at the frog neuromuscular junction. J Physiol. (1998) Cerca con Google

Bradke F, Fawcett JW, Spira ME. Assembly of a new growth cone after axotomy: the precursor to axon regeneration. Nat Rev Neurosci. (2012) Cerca con Google

Brill MS, Lichtman JW, Thompson W, Zuo Y, & Misgeld T. Spatial constraints dictate glial territories at murine neuromuscular junctions. J Cell Biol (2011). Cerca con Google

Brown MC, Hopkins WG.Role of degenerating axon pathways in regeneration of mouse soleus motor axons. J Physiol. (1981) Cerca con Google

Burden SJ, Sargent PB, McMahan UJ. Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve. J Cell Biol. (1979) Cerca con Google

Buschow SI, Nolte-'t Hoen EN, van Niel G, Pols MS, ten Broeke T, Lauwen M, Ossendorp F, Melief CJ, Raposo G, Wubbolts R, Wauben MH, Stoorvogel W. MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic. (2009) Cerca con Google

Capogna M, Gähwiler BH, & Thompson SM. Calcium-independent actions of alpha-latrotoxin on spontaneous and evoked synaptic transmission in the hippocampus. J Neurophysiol. (1996) Cerca con Google

Chen ZL, Strickland S. Laminin gamma1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve. J Cell Biol. (2003) Cerca con Google

Chen F, Qian L, Yang ZH, Huang Y, Ngo ST, Ruan NJ, Wang J, Schneider C, Noakes PG, Ding YQ, Mei L, Luo ZG. Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction. Neuron. (2007) Cerca con Google

Cheng S, Scigalla FP, Speroni di Fenizio P, Zhang ZG, Stolzenburg JU, Neuhaus J. Cerca con Google

ATP enhances spontaneous calcium activity in cultured suburothelial myofibroblasts of the human bladder. PLoS One. (2011) Cerca con Google

Clemence A, Mirsky R, & Jessen KR. Non-myelin-forming Schwann cells proliferate rapidly during Wallerian degeneration in the rat sciatic nerve. J Neurocytol. (1989) Cerca con Google

Coleman M. Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci. (2005) Cerca con Google

Collet C, Strube C, Csernoch L, Mallouk N, Ojeda C, Allard B, Jacquemond V. Effects of extracellular ATP on freshly isolated mouse skeletal muscle cells during pre-natal and postnatal development. Pflugers Arch. (2002) Cerca con Google

Conforti L, Gilley J, Coleman MP. Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci. (2014) Cerca con Google

Descarries LM, Cai S, Robitaille R, Josephson EM, Morest DK. Localization and characterization of nitric oxide synthase at the frog neuromuscular junction. J Neurocytol. (1998) Cerca con Google

Duan ZG, Yan XJ, He XZ, Zhou H, Chen P, Cao R, Xiong JX, Hu WJ, Wang XC, Liang SP.Extraction and protein component analysis of venom from the dissected venom glands of Latrodectus tredecimguttatus. Comp Biochem Physiol B Biochem Mol Biol. (2006) Cerca con Google

Doyu M, Sobue G, Ken E, Kimata K, Shinomura T, Yamada Y, Mitsuma T, Takahashi A. Laminin A, B1, and B2 chain gene expression in transected and regenerating nerves: regulation by axonal signals. J Neurochem. (1993) Cerca con Google

Duregotti E, Tedesco E, Montecucco C, Rigoni M. Calpains participate in nerve terminal degeneration induced by spider and snake presynaptic neurotoxins. Toxicon. (2013) Cerca con Google

Duregotti E, Negro S, Scorzeto M, Zornetta I, Dickinson BC, Chang CJ, Montecucco C, Rigoni M. Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells. Proc Natl Acad Sci U S A. (2015) Cerca con Google

Erez H, Malkinson G, Prager-Khoutorsky M, De Zeeuw CI, Hoogenraad CC, Spira ME. Formation of microtubule-based traps controls the sorting and concentration of vesicles to restricted sites of regenerating neurons after axotomy. J. Cell Biol. (2007). Cerca con Google

Fields R.D. and Burnstock D. Purinergic signalling in neuron–glia interactions. Nature Reviews Neuroscience (2006) Cerca con Google

Filbin M. T. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat. Rev. Neurosci.(2003). Cerca con Google

Gaudet AD, Popovich PG, Ramer MS. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. J Neuroinflammation. (2011) Cerca con Google

Glass JD, Culver DG, Levey AI, Nash NR. Very early activation of m-calpain in peripheral nerve during Wallerian degeneration. J Neurol Sci. (2002) Cerca con Google

Gordon T. The role of neurotrophic factors in nerve regeneration. Neurosurg Focus. (2009) Cerca con Google

Griffin J. W, George R, Ho T. Macrophage systems in peripheral nerves. A review. J. Neuropathol. Exp. Neurol. (1993). Cerca con Google

Grishin EV. Black widow spider toxins: the present and the future. Toxicon. (1998) Cerca con Google

Grishin S, Shakirzyanova A, Giniatullin A, Afzalov R, Giniatullin R. Mechanisms of ATP action on motor nerve terminals at the frog neuromuscular junction. Eur J Neurosci. (2005) Cerca con Google

Hassan SM, Jennekens FG, Veldman H, Oestreicher BA. GAP-43 and p75NGFR immunoreactivity in presynaptic cells following neuromuscular blockade by botulinum toxin in rat. JNeurocytol. (1994) Cerca con Google

Heskamp A, Leibinger M, Andreadaki A, Gobrecht P, Diekmann H, Fischer D. CXCL12/SDF-1 facilitates optic nerve regeneration. Neurobiol Dis. (2013) Cerca con Google

Hoke A, Gordon T, Zochodne D. W, Sulaiman, O. A. A decline in glial cell line derived neurotrophic factor expression is associated with impaired regeneration after long-term Schwann cell denervation. Exp. Neurol. 173, 77–85 (2002). Cerca con Google

Holness CL, Simmons DL. Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood. (1993) Cerca con Google

Jessen KR, Mirsky R, Lloyd AC. Schwann Cells: Development and Role in Nerve Repair. Cerca con Google

Cold Spring Harb Perspect Biol. (2015) Cerca con Google

Klarenbeek J, Goedhart J, van Batenburg A, Groenewald D, Jalink K. Fourth-Generation Epac-Based FRET Sensors for cAMP Feature Exceptional Brightness, Photostability and Dynamic Range: Characterization of Dedicated Sensors for FLIM, for Ratiometry and with High Affinity. Plos One (2015) Cerca con Google

Knott E.P, Assi M, Pearse D.D. Cyclic AMP Signaling: A Molecular Determinant of Peripheral Nerve Regeneration. BioMed Research International Volume (2014) Cerca con Google

Lemons ML, Barua S, Abanto ML, Halfter W, Condic ML. Adaptation of sensory neurons to hyalectin and decorin proteoglycans. J Neurosci. (2005) Cerca con Google

Levi G, Aloisi F, Ciotti MT, Gallo V. Autoradiographic localization and depolarization-induced release of acidic amino acids in differentiating cerebellar granule cell cultures. Brain Res (1984). Cerca con Google

Li M, Ransohoff RM. Multiple roles of chemokine CXCL12 in the central nervous system: a migration from immunology to neurobiology. Prog Neurobiol. (2008) Cerca con Google

Lopez-Verrilli MA, Picou F, Court FA. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia. (2013) Cerca con Google

Love FM, Thompson WJ. Glial cells promote muscle reinnervation by responding to activity-dependent postsynaptic signals. J Neurosci. (1999) Cerca con Google

McGrath KE, Koniski AD, Maltby KM, McGann JK, Palis J. Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Dev Biol. (1999) Cerca con Google

Mallon BS, Shick HE, Kidd GJ, Macklin WB. Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical development. J Neurosci (2002). Cerca con Google

Mathivanan S, Fahner CJ, Reid GE, Simpson RJ. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res. (2012) Cerca con Google

Matteoli M, Haimann C, Torri-Tarelli F, Polak JM, Ceccarelli B, De Camilli P. Differential effect of alpha-latrotoxin on exocytosis from small synaptic vesicles and from large dense-core vesicles containing calcitonin gene-related peptide at the frog neuromuscular junction. Proc Natl Acad Sci U S A (1988) Cerca con Google

McMahan UJ, Wallace BG. Molecules in basal lamina that direct the formation of synaptic specializations at neuromuscular junctions. Dev Neurosci. (1989) Cerca con Google

Mehta A, Reynolds ML, Woolf CJ. Partial denervation of the medial gastrocnemius muscle results in growth-associated protein-43 immunoreactivity in sprouting axons and Schwann cells. Neuroscience. (1993) Cerca con Google

Moloney EB, de Winter F, Verhaagen J. ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease. Front Neurosci. (2014) Cerca con Google

Nagasawa T. CXC chemokine ligand 12 (CXCL12) and its receptor CXCR4. J Mol Med (Berl). (2014) Cerca con Google

Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokinePBSF/SDF-1. Nature. (1996) Cerca con Google

Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci U S A. (1994) Cerca con Google

Nobile M, Monaldi I, Alloisio S, Cugnoli C, Ferroni S. ATP-induced, sustained calcium signalling in cultured rat cortical astrocytes: evidence for a non-capacitative, P2X7-like-mediated calcium entry. FEBS Lett. (2003) Cerca con Google

Opatz J, Küry P, Schiwy N, Järve A, Estrada V, Brazda N, Bosse F, Müller HW. Cerca con Google

SDF-1 stimulates neurite growth on inhibitory CNS myelin. Mol Cell Neurosci. (2009) Cerca con Google

Orlova EV, Rahman MA, Gowen B, Volynski KE, Ashton AC, Manser C, van Heel M, Ushkaryov YA.Structure of alpha-latrotoxin oligomers reveals that divalent cation-dependent tetramers form membrane pores Nat Struct Biol. (2000) Cerca con Google

Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. (2010) Cerca con Google

Park JW, Vahidi B, Taylor AM, Rhee SW, Jeon NL. Microfluidic culture platform for neuroscience research. Nat Protoc. (2006) Cerca con Google

Perrin FE, Lacroix S, Avilés-Trigueros M, David S .Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and interleukin-1beta in Wallerian degeneration. Brain. (2005) Cerca con Google

Piccioli P, Rubartelli A. The secretion of IL-1β and options for release. Semin Immunol. (2013) Cerca con Google

Pinard A, Lévesque S, Vallée J, Robitaille R. Glutamatergic modulation of synaptic plasticity at a PNS vertebrate cholinergic synapse. Eur J Neurosci. (2003) Cerca con Google

Press C, Milbrandt J. Nmnat delays axonal degeneration caused by mitochondrial and oxidative stress. J. Neurosci. (2008). Cerca con Google

Previtali SC, Feltri ML, Archelos JJ, Quattrini A, Wrabetz L, Hartung H. Role of integrins in the peripheral nervous system. Prog Neurobiol. (2001) Cerca con Google

Pryzwansky KB, Kidao S, Merricks EP. Compartmentalization of PDE-4 and cAMP-dependent protein kinase in neutrophils and macrophages during phagocytosis. Cellular biochemistry and biophysics. (1998) Cerca con Google

Pujol F, Kitabgi P, Boudin H. The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons. J Cell Sci. (2005) Cerca con Google

Ramprasad MP, Terpstra V, Kondratenko N, Quehenberger O, Steinberg D. Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein. Proc Natl Acad Sci U S A. (1996) Cerca con Google

Reddy LV, Koirala S, Sugiura Y, Herrera AA, Ko CP. Glial cells maintain synaptic structure and function and promote development of the neuromuscular junction in vivo. Neuron. (2003) Cerca con Google

Reynolds ML, Woolf CJ. Terminal Schwann cells elaborate extensive processes following denervation of the motor endplate. J Neurocytol. (1992) Cerca con Google

Rigoni M, Schiavo G, Weston AE, Caccin P, Allegrini F, Pennuto M, Valtorta F, Montecucco C, Rossetto O. Snake presynaptic neurotoxins with phospholipase A2 activity induce punctate swellings of neurites and exocytosis of synaptic vesicles. J Cell Sci. (2004) Cerca con Google

Rigoni M, Caccin P, Gschmeissner S, Koster G, Postle AD, Rossetto O, Schiavo G, Montecucco C.Equivalent effects of snake PLA2 neurotoxins and lysophospholipid-fatty acid mixtures. Science (2005). Cerca con Google

Rigoni M, Pizzo P, Schiavo G, Weston AE, Zatti G, Caccin P, Rossetto O, Pozzan T, Montecucco C. Calcium influx and mitochondrial alterations at synapses exposed to snake neurotoxins or their phospholipid hydrolysis products. J Biol Chem. (2007) Cerca con Google

Riley DA. Spontaneous elimination of nerve terminals from the endplates of developing skeletal myofibers. Brain Res. (1977) Cerca con Google

Robitaille R. Purinergic receptors and their activation by endogenous purines at perisynaptic glial cells of the frog neuromuscular junction. J Neurosci. (1995) Cerca con Google

Robitaille R, Bourque MJ, Vandaele S. Localization of L-type Ca2+ channels at perisynaptic glial cells of the frog neuromuscular junction. J Neurosci. (1996) Cerca con Google

Robitaille R, Jahromi BS, Charlton MP. Muscarinic Ca2+ responses resistant to muscarinic antagonists at perisynaptic Schwann cells of the frog neuromuscular junction. J Physiol. (1997) Cerca con Google

Rochon D, Rousse I, Robitaille R. Synapse-glia interactions at the mammalian neuromuscular junction. J Neurosci. (2001) Cerca con Google

Rotshenker, S. Wallerian degeneration: the innate-immune response to traumatic nerve injury. J. Neuroinflammation 8, 109 (2011). Cerca con Google

Rudolf R, Khan MM, Labeit S, Deschenes MR. Degeneration of neuromuscular junction in age and dystrophy. Front Aging Neurosci. 2014 Cerca con Google

Sanes JR, Lichtman JW. Development of the vertebrate neuromuscular junction. Annu Rev Neurosci. (1999) Cerca con Google

Silinsky EM. On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals. J Physiol. (1975) Cerca con Google

Simons M, Raposo G. Exosomes--vesicular carriers for intercellular communication. Curr Opin Cell Biol. (2009) Cerca con Google

Schaefer AW, Schoonderwoert VT, Ji L, Mederios N, Danuser G, Forscher P.. Coordination of actin filament and microtubule dynamics during neurite outgrowth. Dev. Cell (2008). Cerca con Google

Scheer H, Prestipino G, Meldolesi J. Reconstitution of the purified alpha-latrotoxin receptor in liposomes and planar lipid membranes. Clues to the mechanism of toxin action. Cerca con Google

EMBO J. (1986) Cerca con Google

Shaywitz AJ, Greenberg ME. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem. (1999) Cerca con Google

Scheib J, Höke A. Advances in peripheral nerve regeneration. Nat Rev Neurol. (2013) Cerca con Google

Shen, Y. J., DeBellard, M. E., Salzer, J. L., Roder, J. & Filbin, M. T. Myelin-associated glycoprotein in myelin and expressed by Schwann cells inhibits axonal regeneration and branching. Mol. Cell. Neurosci. (1998). Cerca con Google

Simpson RJ, Jensen SS, Lim JW. Proteomic profiling of exosomes: current perspectives. Proteomics. (2008) Cerca con Google

Son YJ & Thompon WJ. Schwann cell processes guide regeneration of peripheral axons. Neuron. (1995) Cerca con Google

Son YJ & Thompson WJ. Nerve sprouting in muscle is induced and guided by processes extended by Schwann cells. Neuron. (1995). Cerca con Google

Son YJ, Trachtenberg JT, Thompson WJ. Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions. Trends Neurosci. (1996) Cerca con Google

Song JW, Misgeld T, Kang H, Knecht S, Lu J, Cao Y, Cotman SL, Bishop DL, Lichtman JW.. Lysosomal activity associated with developmental axon pruning. J Neurosci. (2008) Cerca con Google

Sotelo-Silveira, J. R., Calliari, A., Kun, A., Koenig, E. & Sotelo, J. R. RNA trafficking in axons. Traffic (2006). Cerca con Google

Stoll G, Griffin JW, Li CY, Trapp BD. Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation. J Neurocytol. (1989) Cerca con Google

Stoll G, Jander S, Myers RR. Degeneration and regeneration of the peripheral nervous system: from Augustus Waller's observations to neuroinflammation. J Peripher Nerv Syst. (2002) Cerca con Google

Subang MC, Richardson PM. Influence of injury and cytokines on synthesis of monocyte chemoattractant protein-1 mRNA in peripheral nervous tissue. Eur J Neurosci. (2001) Cerca con Google

Tedesco E, Rigoni M, Caccin P, Grishin E, Rossetto O, Montecucco C. Calcium overload in nerve terminals of cultured neurons intoxicated by alpha-latrotoxin and snake PLA2 neurotoxins. Toxicon. (2009) Cerca con Google

Tetta C, Ghigo E, Silengo L, Deregibus MC, Camussi G. Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine. (2013) Cerca con Google

Todd KJ, Robitaille R. Neuron-glia interactions at the neuromuscular synapse. Novartis Found Symp. 2006 Cerca con Google

Tofaris GK, Patterson PH, Jessen KR, Mirsky R. Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF. J Neurosci. (2002) Cerca con Google

Tucker BA, Mearow KM. Peripheral sensory axon growth: from receptor binding to cellular signaling. Can J Neurol Sci. (2008) Cerca con Google

Ushkaryov YA, Rohou A, & Sugita S. Alpha-Latrotoxin and its receptors. Handb Exp Pharmacol. (2008) Cerca con Google

Van Niel G, Porto-Carreiro I, Simoes S, Raposo G. Exosomes: a common pathway for a specialized function. J Biochem. (2006) Cerca con Google

Vargas ME, Barres BA. Why is Wallerian degeneration in the CNS so slow? Annu Rev Neurosci. (2007) Cerca con Google

Volynski KE, Capogna M, Ashton AC, Thomson D, Orlova EV, Manser CF, Ribchester RR, Ushkaryov YA .Mutant alpha-latrotoxin (LTXN4C) does not form pores and causes secretion by receptor stimulation: this action does not require neurexins. J Biol Chem. 2003 Cerca con Google

Vrbova G, Mehra N, Shanmuganathan H, Tyreman N, Schachner M, Gordon T. Chemical communication between regenerating motor axons and Schwann cells in the growth pathway. Cerca con Google

Eur J Neurosci. (2009) Cerca con Google

Wallquist W, Patarroyo M, Thams S, Carlstedt T, Stark B, Cullheim S, Hammarberg H. Laminin chains in rat and human peripheral nerve: distribution and regulation during development and after axonal injury. J Comp Neurol. (2002) Cerca con Google

Wolpowitz D, Mason TB, Dietrich P, Mendelsohn M, Talmage DA, Role LW. Cerca con Google

Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron. (2000) Cerca con Google

Wood SJ, Slater CR. Safety factor at the neuromuscular junction. Prog Neurobiol. (2001) Cerca con Google

Woolf CJ, Reynolds ML, Chong MS, Emson P, Irwin N, Benowitz LI. Denervation of the motor endplate results in the rapid expression by terminal Schwann cells of the growth-associated protein GAP-43. J Neurosci. (1992) Cerca con Google

Yan F, Wu X, Crawford M, Duan W, Wilding EE, Gao L, Nana-Sinkam SP, Villalona-Calero MA, Baiocchi RA, Otterson GA.The Search for an Optimal DNA, RNA, and Protein Detection by in situ Hybridization, Immunohistochemistry, and Solution-Based Methods. Methods. (2010) Cerca con Google

Ydens E, Cauwels A, Asselbergh B, Goethals S, Peeraer L, Lornet G, Almeida-Souza L, Van Ginderachter JA, Timmerman V, Janssens S.. Acute injury in the peripheral nervous system triggers an alternative macrophage response. J. Neuroinflammation. (2012). Cerca con Google

Yoo, S., van Niekerk, E. A., Merianda, T. T. & Twiss, J. L. Dynamics of axonal mRNA transport and implications for peripheral nerve regeneration. Exp. Neurol. (2010). Cerca con Google

You, S., Petrov, T., Chung, P. H. & Gordon, T. The expression of the low affinity nerve growth factor receptor in long-term denervated Schwann cells. Glia 20, 87–100 (1997). Cerca con Google

Yu B, Zhou S, Yi S, Gu X.The regulatory roles of non-coding RNAs in nerve injury and regeneration. Prog Neurobiol. (2015) Cerca con Google

Yurchenco PD, Cheng YS, Campbell K, Li S. Loss of basement membrane, receptor and cytoskeletal lattices in a laminin-deficient muscular dystrophy. J Cell Sci. (2004) Cerca con Google

Zhu Y, Matsumoto T, Mikami S, Nagasawa T, Murakami F. SDF1/CXCR4 signalling regulates two distinct processes of precerebellar neuronal migration and its depletion leads to abnormal pontine nuclei formation. Development. (2009) Cerca con Google

Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Cerca con Google

Immunity. (2000) Cerca con Google

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