Artículo

Este artículo es de Acceso Abierto y puede ser descargado en su versión final desde nuestro repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects particularly motoneurons. Several pieces of evidence suggested the involvement of autoimmune mechanisms mediated by antibodies in ALS. However, the significance of those antibodies in the disease and the underlying mechanisms are unknown. Here we showed that IgG purified from a group of sporadic ALS patients, but not familial ALS patients, specifically interact with the presynaptic membrane of motoneurons through an antigen-antibody interaction and modulated synaptic transmission. Immunoreactivity against nerve terminals showed strong correlation with synaptic modulation ability. In addition, several controls have ruled out the possibility for this synaptic modulation to be mediated through proteases or nonspecific effects. Effective IgG potentiated both spontaneous and asynchronous transmitter release. Application of pharmacological inhibitors suggested that activation of this increased release required a nonconstitutive Ca2+ influx through N-type (Ca v2.2) channels and phospholipase C activity and that activation of IP3 and ryanodine receptors were necessary to both activate and sustain the increased release. Consistent with the notion that ALS is heterogeneous disorder, our results reveal that, in ∼50% of ALS patients, motor nerve terminals constitutes a target for autoimmune response. Copyright © 2006 Society for Neuroscience.

Registro:

Documento: Artículo
Título:Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals
Autor:Pagani, M.R.; Reisin, R.C.; Uchitel, O.D.
Filiación:Laboratorio de Fisiología Y Biología Molecular, Instituto de Fisiología Biología Molecular Y Neurociencias UBA-CONICET, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina
Servicio de Neurofisiología, Hospital Británico, C1280AEB Buenos Aires, Argentina
Laboratorio de Fisiología Y Biología Molecular, Facultad de Ciencias Exactas Y Naturales, Pabellón II, C1428EHA Buenos Aires, Argentina
Palabras clave:Calcium channels; Calcium homeostasis alteration; IP3R; Phospholipase C; RyR; Signaling mechanisms; calcium; calcium channel N type; calcium ion; immunoglobulin G; inositol trisphosphate; neurotransmitter; phospholipase C; proteinase; ryanodine receptor; adult; aged; amyotrophic lateral sclerosis; animal tissue; antigen antibody reaction; article; autoimmunity; calcium signaling; calcium transport; clinical article; controlled study; degenerative disease; enzyme activity; human; immune response; immunoreactivity; male; motoneuron; mouse; nerve ending; neuromodulation; neurotransmitter release; nonhuman; presynaptic membrane; priority journal; receptor upregulation; synaptic potential; synaptic transmission; Adult; Aged; Amyotrophic Lateral Sclerosis; Animals; Calcium; Calcium Channel Blockers; Calcium Channels; Calcium Channels, N-Type; Calcium Signaling; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; Enzyme Inhibitors; Evoked Potentials; Female; Humans; Immunoglobulin G; Immunohistochemistry; Immunoprecipitation; Inositol 1,4,5-Trisphosphate Receptors; Male; Mice; Middle Aged; Muscle Fibers; Neuromuscular Junction; Neurotransmitter Agents; omega-Conotoxin GVIA; Phospholipase C; Presynaptic Terminals; Receptors, Cytoplasmic and Nuclear; Ryanodine Receptor Calcium Release Channel; Statistics; Synaptic Transmission; Time Factors
Año:2006
Volumen:26
Número:10
Página de inicio:2661
Página de fin:2672
DOI: http://dx.doi.org/10.1523/JNEUROSCI.4394-05.2006
Título revista:Journal of Neuroscience
Título revista abreviado:J. Neurosci.
ISSN:02706474
CODEN:JNRSD
CAS:calcium ion, 14127-61-8; calcium, 7440-70-2; immunoglobulin G, 97794-27-9; inositol trisphosphate, 27121-73-9; phospholipase C, 9001-86-9; proteinase, 9001-92-7; Cacna1b protein, mouse; Calcium Channel Blockers; Calcium Channels; Calcium Channels, N-Type; Calcium, 7440-70-2; Enzyme Inhibitors; Immunoglobulin G; Inositol 1,4,5-Trisphosphate Receptors; ITPR1 protein, human; Neurotransmitter Agents; omega-Conotoxin GVIA, 92078-76-7; Phospholipase C, EC 3.1.4.3; Receptors, Cytoplasmic and Nuclear; Ryanodine Receptor Calcium Release Channel
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_02706474_v26_n10_p2661_Pagani.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v26_n10_p2661_Pagani

Referencias:

  • Andjus, P.R., Stevic-Marinkovic, Z., Cherubini, E., Immunoglobulins from motoneurone disease patients enhance glutamate release from rat hippocampal neurones in culture (1997) J Physiol, 504, pp. 103-112. , Lond
  • Angleson, J.K., Betz, W.J., Intraterminal Ca2+ and spontaneous transmitter release at the frog neuromuscular junction (2001) J Neurophysiol, 85, pp. 287-294
  • Arsac, C., Raymond, C., Martin-Moutot, N., Dargent, B., Couraud, F., Pouget, J., Seagar, M., Immunoassays fail to detect antibodies against neuronal calcium channels in amyotrophic lateral sclerosis serum (1996) Ann Neurol, 40, pp. 695-700
  • Athanassakis, I., Protopapadakis, E., Vassiliadis, S., Localization of pepstatin's inhibitory action during Fc-mediated antibody internalization: Possible implications for antibody-mediated viral transmission (2000) Cell Immunol, 199, pp. 81-88
  • Berridge, M.J., Bootman, M.D., Roderick, H.L., Calcium signalling: Dynamics, homeostasis and remodelling (2003) Nat Rev Mol Cell Biol, 4, pp. 517-529
  • Brooks, B.R., Shodis, K.A., Lewis, D.H., Rawling, J.D., Sanjak, M., Belden, D.S., Hakim, H., Gaffney, J.M., Natural history of amyotrophic lateral sclerosis. Quantification of symptoms, signs, strength, and function (1995) Adv Neurol, 68, pp. 163-184
  • Bullens, R.W., O'Hanlon, G.M., Wagner, E., Molenaar, P.C., Furukawa, K., Plomp, J.J., Willison, H.J., Complex gangliosides at the neuromuscular junction are membrane receptors for autoantibodies and botulinum neurotoxin but redundant for normal synaptic function (2002) J Neurosci, 22, pp. 6876-6884
  • Chio, A., Benzi, G., Dossena, M., Mutani, R., Mora, G., Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players (2005) Brain, 128, pp. 472-476
  • Cleveland, D.W., Rothstein, J.D., From Charcot to Lou Gehrig: Deciphering selective motor neuron death in ALS (2001) Nat Rev Neurosci, 2, pp. 806-819
  • Cui, L.Y., Liu, M.S., Tang, X.F., Single fiber electromyography in 78 patients with amyotrophic lateral sclerosis (2004) Chin Med J (Engl), 117, pp. 1830-1833
  • David, G., Barrett, E.F., Mitochondrial Ca2+ uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals (2003) J Physiol, 548, pp. 425-438. , Lond
  • Day, N.C., Wood, S.J., Ince, P.G., Volsen, S.G., Smith, W., Slater, C.R., Shaw, P.J., Differential localization of voltage-dependent calcium channel α1 subunits at the human and rat neuromuscular junction (1997) J Neurosci, 17, pp. 6226-6235
  • Delbono, O., Garcia, J., Appel, S.H., Stefani, E., Calcium current and charge movement of mammalian muscle: Action of amyotrophic lateral sclerosis immunoglobulins (1991) J Physiol, 444, pp. 723-742. , Lond
  • Demestre, M., Pullen, A., Orrell, R.W., Orth, M., ALS-IgG-induced selective motor neurone apoptosis in rat mixed primary spinal cord cultures (2005) J Neurochem, 94, pp. 268-275
  • Doughty, S.W., Blaney, F.E., Orlek, B.S., Richards, W.G., A molecular mechanism for toxin block in N-type calcium channels (1998) Protein Eng, 11, pp. 95-99
  • Drachman, D.B., Does autoimmunity play a role in amyotrophic lateral sclerosis? (2000) Amyotrophic Lateral Sclerosis, pp. 327-339. , Brown RH, Meininger V, Swash M, eds, London: Dunitz
  • Engelhardt, J.I., Siklos, L., Komuves, L., Smith, R.G., Appel, S.H., Antibodies to calcium channels from ALS patients passively transferred to mice selectively increase intracellular calcium and induce ultrastructural changes in motoneurons (1995) Synapse, 20, pp. 185-199
  • Engelhardt, J.I., Siklos, L., Appel, S.H., Altered calcium homeostasis and ultrastructure in motoneurons of mice caused by passively transferred anti-motoneuronal IgG (1997) J Neuropathol Exp Neurol, 56, pp. 21-39
  • Fratantoni, S.A., Weisz, G., Pardal, A.M., Reisin, R.C., Uchitel, O.D., Amyotrophic lateral sclerosis IgG-treated neuromuscular junctions develop sensitivity to L-type calcium channel blocker (2000) Muscle Nerve, 23, pp. 543-550
  • Guegan, C., Vila, M., Rosoklija, G., Hays, A.P., Przedborski, S., Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic lateral sclerosis (2001) J Neurosci, 21, pp. 6569-6576
  • Hua, S.Y., Raciborska, D.A., Trimble, W.S., Charlton, M.P., Different VAMP/synaptobrevin complexes for spontaneous and evoked transmitter release at the crayfish neuromuscular junction (1998) J Neurophysiol, 80, pp. 3233-3246
  • Jayaraman, T., Marks, A.R., T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to apoptosis (1997) Mol Cell Biol, 17, pp. 3005-3012
  • Katz, E., Protti, D.A., Ferro, P.A., Rosato Siri, M.D., Uchitel, O.D., Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction (1997) Br J Pharmacol, 121, pp. 1531-1540
  • Kimura, F., Smith, R.G., Delbono, O., Nyormoi, O., Schneider, T., Nastainczyk, W., Hofmann, F., Appel, S.H., Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel alpha 1 subunit (1994) Ann Neurol, 35, pp. 164-171
  • Llinas, R., Sugimori, M., Cherksey, B.D., Smith, R.G., Delbono, O., Stefani, E., Appel, S., IgG from amyotrophic lateral sclerosis patients increases current through P-type calcium channels in mammalian cerebellar Purkinje cells and in isolated channel protein in lipid bilayer (1993) Proc Natl Acad Sci, 90, pp. 11743-11747. , USA
  • Maselli, R.A., Wollman, R.L., Leung, C., Distad, B., Palombi, S., Richman, D.P., Salazar-Grueso, E.F., Roos, R.P., Neuromuscular transmission in amyotrophic lateral sclerosis (1993) Muscle Nerve, 16, pp. 1193-1203
  • McEnery, M.W., Snowman, A.M., Snyder, S.H., The association of endogenous Go alpha with the purified omega-conotoxin GVIA receptor (1994) J Biol Chem, 269, pp. 5-8
  • Medesan, C., Cianga, P., Mummert, M., Stanescu, D., Ghetie, V., Ward, E.S., Comparative studies of rat IgG to further delineate the Fc:FcRn interaction site (1998) Eur J Immunol, 28, pp. 2092-2100
  • Mochida, S., Sheng, Z.H., Baker, C., Kobayashi, H., Catterall, W.A., Inhibition of neurotransmission by peptides containing the synaptic protein interaction site of N-type Ca2+ channels (1996) Neuron, 17, pp. 781-788
  • Mohamed, H.A., Mosier, D.R., Zou, L.L., Siklos, L., Alexianu, M.E., Engelhardt, J.I., Beers, D.R., Appel, S.H., Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons (2002) J Neurosci Res, 69, pp. 110-116
  • Mosier, D.R., Baldelli, P., Delbono, O., Smith, R.G., Alexianu, M.E., Appel, S.H., Stefani, E., Amyotrophic lateral sclerosis immunoglobulins increase Ca2+ currents in a motoneuron cell line (1995) Ann Neurol, 37, pp. 102-109
  • Mosier, D.R., Siklos, L., Appel, S.H., Resistance of extraocular motoneuron terminals to effects of amyotrophic lateral sclerosis sera (2000) Neurology, 54, pp. 252-255
  • Muchnik, S., Losavio, A., Lorenzo, S.D., Effect of amyotrophic lateral sclerosis serum on calcium channels related to spontaneous acetylcholine release (2002) Clin Neurophysiol, 113, pp. 1066-1071
  • Narita, K., Akita, T., Hachisuka, J., Huang, S., Ochi, K., Kuba, K., Functional coupling of Ca2+ channels to ryanodine receptors at presynaptic terminals. Amplification of exocytosis and plasticity (2000) J Gen Physiol, 115, pp. 519-532
  • Norris Jr., F.H., Gasteiger, E.L., Action potentials of single motor units in normal muscle (1955) Electroencephalogr Clin Neurophysiol Suppl, 7, pp. 115-125
  • Nyormoi, O., Proteolytic activity in amyotrophic lateral sclerosis IgG preparations (1996) Ann Neurol, 40, pp. 701-706
  • Ober, R.J., Radu, C.G., Ghetie, V., Ward, E.S., Differences in promiscuity for antibody-FcRn interactions across species: Implications for therapeutic antibodies (2001) Int Immunol, 13, pp. 1551-1559
  • Offen, D., Halevi, S., Orion, D., Mosberg, R., Stern-Goldberg, H., Melamed, E., Atlas, D., Antibodies from ALS patients inhibit dopamine release mediated by L-type calcium channels (1998) Neurology, 51, pp. 1100-1103
  • Ordonez, G., Sotelo, J., Antibodies against fetal muscle proteins in serum from patients with amyotrophic lateral sclerosis (1989) Neurology, 39, pp. 683-686
  • Orrenius, S., Zhivotovsky, B., Nicotera, P., Regulation of cell death: The calcium-apoptosis link (2003) Nat Rev Mol Cell Biol, 4, pp. 552-565
  • O'Shaughnessy, T.J., Yan, H., Kim, J., Middlekauff, E.H., Lee, K.W., Phillips, L.H., Kim, Y.I., Amyotrophic lateral sclerosis: Serum factors enhance spontaneous and evoked transmitter release at the neuromuscular junction (1998) Muscle Nerve, 21, pp. 81-90
  • Otsu, Y., Murphy, T.H., Optical postsynaptic measurement of vesicle release rates for hippocampal synapses undergoing asynchronous release during train stimulation (2004) J Neurosci, 24, pp. 9076-9086
  • Pagani, R., Song, M., McEnery, M., Qin, N., Tsien, R.W., Toro, L., Stefani, E., Uchitel, O.D., Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca 2+ channel knockout mouse (2004) Neuroscience, 123, pp. 75-85
  • Protti, D.A., Szczupak, L., Scornik, F.S., Uchitel, O.D., Effect of omega-conotoxin GVIA on neurotransmitter release at the mouse neuromuscular junction (1991) Brain Res, 557, pp. 336-339
  • Pullen, A.H., Humphreys, P., Ultrastructural analysis of spinal motoneurones from mice treated with IgG from ALS patients, healthy individuals, or disease controls (2000) J Neurol Sci, 180, pp. 35-45
  • Pullen, A.H., Demestre, M., Howard, R.S., Orrell, R.W., Passive transfer of purified IgG from patients with amyotrophic lateral sclerosis to mice results in degeneration of motor neurons accompanied by Ca2+ enhancement (2004) Acta Neuropathol, 107, pp. 35-46. , Berl
  • Rizzoli, S.O., Betz, W.J., Effects of 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one on synaptic vesicle cycling at the frog neuromuscular junction (2002) J Neurosci, 22, pp. 10680-10689
  • Rizzuto, R., Brini, M., Murgia, M., Pozzan, T., Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria (1993) Science, 262, pp. 744-747
  • Robidoux, J., Simoneau, L., St-Pierre, S., Ech-Chadli, H., Lafond, J., Human syncytiotrophoblast NPY receptors are located on BBM and activate PLC-to-PKC axis (1998) Am J Physiol, 274, pp. E502-E509
  • Sara, Y., Virmani, T., Deak, F., Liu, X., Kavalali, E.T., An isolated pool of vesicles recycles at rest and drives spontaneous neurotransmission (2005) Neuron, 45, pp. 563-573
  • Schiavo, G., Gu, Q.M., Prestwich, G.D., Sollner, T.H., Rothman, J.E., Calcium-dependent switching of the specificity of phosphoinositide binding to synaptotagmin (1996) Proc Natl Acad Sci, 93, pp. 13327-13332. , USA
  • Siklos, L., Engelhardt, J., Harati, Y., Smith, R.G., Joo, F., Appel, S.H., Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis (1996) Ann Neurol, 39, pp. 203-216
  • Smith, R.G., Hamilton, S., Hofmann, F., Schneider, T., Nastainczyk, W., Birnbaumer, L., Stefani, E., Appel, S.H., Serum antibodies to L-type calcium channels in patients with amyotrophic lateral sclerosis (1992) N Engl J Med, 327, pp. 1721-1728
  • Smith, R.G., Alexianu, M.E., Crawford, G., Nyormoi, O., Stefani, E., Appel, S.H., Cytotoxicity of immunoglobulins from amyotrophic lateral sclerosis patients on a hybrid motoneuron cell line (1994) Proc Natl Acad Sci, 91, pp. 3393-3397. , USA
  • Smith, S.A., Miller, R.G., Murphy, J.R., Ringel, S.P., Treatment of ALS with high dose pulse cyclophosphamide (1994) J Neurol Sci [Suppl], 124, pp. 84-87
  • Stoop, R., Poo, M.M., Potentiation of transmitter release by ciliary neurotrophic factor requires somatic signaling (1995) Science, 267, pp. 695-699
  • Strong, M.J., The basic aspects of therapeutics in amyotrophic lateral sclerosis (2003) Pharmacol Ther, 98, pp. 379-414
  • Thomas, M.M., Dunn, S.M., Amyotrophic lateral sclerosis immunoglobulins are ineffective in altering calcium influx through presynaptic voltage-sensitive calcium channels (1997) Neurol Res, 19, pp. 129-134
  • Troost, D., Van Den Oord, J.J., Vianney De Jong, J.M., Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis (1990) Neuropathol Appl Neurobiol, 16, pp. 401-410
  • Uchitel, O.D., Appel, S.H., Crawford, F., Sczcupak, L., Immunoglobulins from amyotrophic lateral sclerosis patients enhance spontaneous transmitter release from motor-nerve terminals (1988) Proc Natl Acad Sci, 85, pp. 7371-7374. , USA
  • Uchitel, O.D., Scornik, F., Protti, D.A., Fumberg, C.G., Alvarez, V., Appel, S.H., Long-term neuromuscular dysfunction produced by passive transfer of amyotrophic lateral sclerosis immunoglobulins (1992) Neurology, 42, pp. 2175-2180
  • Vincent, A., Immunology of the neuromuscular junction and presynaptic nerve terminal (1999) Curr Opin Neurol, 12, pp. 545-551
  • Yan, H.D., Lim, W., Lee, K.W., Kim, J., Sera from amyotrophic lateral sclerosis patients reduce high-voltage activated Ca2+ currents in mice dorsal root ganglion neurons (1997) Neurosci Lett, 235, pp. 69-72
  • Yang, F., He, X., Feng, L., Mizuno, K., Liu, X.W., Russell, J., Xiong, W.C., Lu, B., PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation (2001) Nat Neurosci, 4, pp. 19-28
  • Zhainazarov, A.B., Annunziata, P., Toneatto, S., Cherubini, E., Nistri, A., Serum fractions from amyotrophic lateral sclerosis patients depress voltage-activated Ca2+ currents of rat cerebellar granule cells in culture (1994) Neurosci Lett, 172, pp. 111-114

Citas:

---------- APA ----------
Pagani, M.R., Reisin, R.C. & Uchitel, O.D. (2006) . Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals. Journal of Neuroscience, 26(10), 2661-2672.
http://dx.doi.org/10.1523/JNEUROSCI.4394-05.2006
---------- CHICAGO ----------
Pagani, M.R., Reisin, R.C., Uchitel, O.D. "Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals" . Journal of Neuroscience 26, no. 10 (2006) : 2661-2672.
http://dx.doi.org/10.1523/JNEUROSCI.4394-05.2006
---------- MLA ----------
Pagani, M.R., Reisin, R.C., Uchitel, O.D. "Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals" . Journal of Neuroscience, vol. 26, no. 10, 2006, pp. 2661-2672.
http://dx.doi.org/10.1523/JNEUROSCI.4394-05.2006
---------- VANCOUVER ----------
Pagani, M.R., Reisin, R.C., Uchitel, O.D. Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals. J. Neurosci. 2006;26(10):2661-2672.
http://dx.doi.org/10.1523/JNEUROSCI.4394-05.2006