Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte la política de Acceso Abierto del editor

Abstract:

Background: Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting 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. Objectives: Examine the significance of those antibodies in the synaptic potentiation in motor nerve terminals. Methods: IgG were purified from a group of ALS patients and a group of control individuals. Electrophysiological and pharmacological tools as well as immunohistochemistry were used. Results and Conclusion: 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 (Cav2.2) 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.

Registro:

Documento: Artículo
Título:Mechanisms of synaptic alteration mediated by antibodies from patients with amyotrophic lateral sclerosis
Autor:Pagani, M.R.; Reisin, R.C.; Uchitel, O.D.
Filiación:Laboratorio de Fisiología Y Biología Molecular, IFIBYNE-CONICET, Pabellón II, (C1428EHA)-Buenos Aires, Argentina
Servicio de Neurofisiología, Hospital Británico, (C1280AEB), Buenos Aires, Argentina
Palabras clave:Calcium channels; Calcium homeostasis alteration; IP3R; Phospholipase C; RyR; Signaling mechanisms; calcium channel; immunoglobulin G; phospholipase C; ryanodine receptor; amyotrophic lateral sclerosis; article; calcium homeostasis; electrophysiology; human; immunohistochemistry; immunoreactivity; motor nerve; nerve ending; synaptic transmission
Año:2007
Volumen:32
Número:1
Página de inicio:9
Página de fin:19
Título revista:Revista Neurologica Argentina
Título revista abreviado:Rev. Neurol. Argent.
ISSN:03250938
CODEN:RNARD
CAS:immunoglobulin G, 97794-27-9; phospholipase C, 9001-86-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03250938_v32_n1_p9_Pagani

Referencias:

  • Lomen-Hoerth, C., Murphy, J., Langmore, S., Kramer, J.H., Olney, R.K., Miller, B., Are amyotrophic lateral sclerosis patients cognitively normal? (2003) Neurology, 60, pp. 1094-1097
  • Strong, M.J., Lomen-Hoerth, C., Caselli, R.J., Bigio, E.H., Yang, W., Cognitive impairment, frontotemporal dementia, and the motor neuron diseases (2003) Ann Neurol, 54 (SUPPL. 5), pp. S20-S23
  • Strong, M.J., The basic aspects of therapeutics in amyotrophic lateral sclerosis (2003) Pharmacol Ther, 98, pp. 379-414
  • Ringholz, G.M., Appel, S.H., Bradshaw, M., Cooke, N.A., Mosnik, D.M., Schulz, P.E., Prevalence and patterns of cognitive impairment in sporadic ALS (2005) Neurology, 65, pp. 586-590
  • Mitsuyama, Y., Presenile dementia with motor neuron disease (1993) Dementia, 4, pp. 137-142
  • Mitsuyama, Y., Dementia with motor neuron disease (2000) Neuropathology, 20 (SUPPL.), pp. S79-S81
  • De Carvalho, M., Chio, A., Dengler, R., Hecht, M., Weber, M., Swash, M., Neurophysiological measures in amyotrophic lateral sclerosis: Markers of progression in clinical trials (2005) Amyotroph Lateral Scler Other Motor Neuron Disord, 6, pp. 17-28
  • Drachman, D.B., Fishman, P.S., Rothstein, J.D., Motomura, M., Lang, B., Vincent, A., Amyotrophic lateral sclerosis. An autoimmune disease? (1995) Adv Neurol, 68, pp. 59-65
  • Field, E.J., Hughes, D., Toxicity of motor neurone disease serum for myelin in tissue culture (1965) Br Med J, 5475, pp. 1399-1401
  • Roisen, F.J., Bartfeld, H., Donnenfeld, H., Baxter, J., Neuron specific in vitro cytotoxicity of sera from patients with amyotrophic lateral sclerosis (1982) Muscle Nerve, 5, pp. 48-53
  • 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 USA, 91, pp. 3393-3397
  • Horwich, M.S., Engel, W.K., Chauvin, P.B., Amyotrophic lateral sclerosis sera applied to cultured motor neurons (1974) Arch Neurol, 30, pp. 332-333
  • Liveson, J., Frey, H., Bornstein, M.B., The effect of serum from ALS patients on organotypic nerve and muscle tissue cultures (1975) Acta Neuropathol (Berl), 32, pp. 127-131
  • 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
  • Mulder, D.W., Lambert, E.H., Eaton, L.M., Myasthenic syndrome in patients with amyotrophic lateral sclerosis (1959) Neurology, 9, pp. 627-631
  • Denys, E.H., Norris Jr., F.H., Amyotrophic lateral sclerosis. Impairment of neuromuscular transmission (1979) Arch Neurol, 36, pp. 202-205
  • Maselli, R.A., Wollman, R.L., Leung, C., Distad, B., Palombi, S., Richman, D.P., Neuromuscular transmission in amyotrophic lateral sclerosis (1993) Muscle Nerve, 16, pp. 1193-1203
  • Uchitel, O.D., Appel, S.H., Crawford, F., Sczcupak, L., Immunoglobulins from amyotrophic lateral sclerosis patients enhance spontaneous transmitter release from motornerve terminals (1988) Proc Natl Acad Sci USA, 85, pp. 7371-7374
  • 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
  • Appel, S.H., Engelhardt, J.I., Garcia, J., Stefani, E., Autoimmunity and ALS: A comparison of animal models of immune-mediated motor neuron destruction and human ALS (1991) Adv Neurol, 56, pp. 405-412
  • O'Shaughnessy, T.J., Yan, H., Kim, J., Middlekauff, E.H., Lee, K.W., Phillips, L.H., Amyotrophic lateral sclerosis: Serum factors enhance spontaneous and evoked transmitter release at the neuromuscular junction (1998) Muscle Nerve, 21, pp. 81-90
  • 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
  • Mosier, D.R., Baldelli, P., Delbono, O., Smith, R.G., Alexianu, M.E., Appel, S.H., Amyotrophic lateral sclerosis immunoglobulins increase Ca2+ currents in a motoneuron cell line (1995) Ann Neurol, 37, pp. 102-109
  • 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
  • Carter, J.R., Mynlieff, M., Amyotrophic lateral sclerosis patient IgG alters voltage dependence of Ca2+ channels in dissociated rat motoneurons (2003) Neurosci Lett, 353, pp. 221-225
  • Arsac, C., Raymond, C., Martin-Moutot, N., Dargent, B., Couraud, F., Pouget, J., Immunoassays fail to detect antibodies against neuronal calcium channels in amyotrophic lateral sclerosis serum (1996) Ann Neurol, 40, pp. 695-700
  • 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
  • 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
  • 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
  • McGeer, E.G., McGeer, P.L., Pharmacologic approaches to the treatment of amyotrophic lateral sclerosis (2005) BioDrugs, 19, pp. 31-37
  • 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
  • Brooks, B.R., Escorial, E., World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial "Clinical limits of amyotrophic lateral sclerosis" workshop contributors (1994) J Neurol Sci, 124 (SUPPL.), pp. 96-107
  • Miyamoto, M.D., Binomial analysis of quantal transmitter release at glycerol treated frog neuromuscular junctions (1975) J Physiol, 250, pp. 121-142
  • Katz, B., Miledi, R., The role of calcium in neuromuscular facilitation (1968) J Physiol, 195, pp. 481-492
  • Magleby, K.L., Stevens, C.F., A quantitative description of end-plate currents (1972) J Physiol, 223, pp. 173-197
  • 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 (2006) J Neurosci, 26, pp. 2661-2672
  • Pagani, R., Song, M., McEnery, M., Qin, N., Tsien, R.W., Toro, L., Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout mouse (2004) Neuroscience, 123, pp. 75-85
  • Nyormoi, O., Proteolytic activity in amyotrophic lateral sclerosis IgG preparations (1996) Ann Neurol, 40, pp. 701-706
  • Narita, K., Akita, T., Hachisuka, J., Huang, S., Ochi, K., Kuba, K., Functional coupling of Ca(2+) channels to ryanodine receptors at presynaptic terminals. Amplification of exocytosis and plasticity (2000) J Gen Physiol, 115, pp. 519-532
  • Day, N.C., Wood, S.J., Ince, P.G., Volsen, S.G., Smith, W., Slater, C.R., Differential localization of voltage-dependent calcium channel alpha1 subunits at the human and rat neuromuscular junction (1997) J Neurosci, 17, pp. 6226-6235
  • Kawamata, T., Akiyama, H., Yamada, T., McGeer, P.L., Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue (1992) Am J Pathol, 140, pp. 691-707
  • Smith, R.G., Hamilton, S., Hofmann, F., Schneider, T., Nastainczyk, W., Birnbaumer, L., Serum antibodies to L-type calcium channels in patients with amyotrophic lateral sclerosis (1992) N Engl J Med, 327, pp. 1721-1728
  • Vincent, A., Immunology of the neuromuscular junction and presynaptic nerve terminal (1999) Curr Opin Neurol, 12, pp. 545-551
  • Bullens, R.W., O'Hanlon, G.M., Wagner, E., Molenaar, P.C., Furukawa, K., Plomp, J.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
  • 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
  • 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
  • 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
  • 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
  • Orrenius, S., Zhivotovsky, B., Nicotera, P., Regulation of cell death: The calcium-apoptosis link (2003) Nat Rev Mol Cell Biol, 4, pp. 552-565
  • 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
  • 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
  • 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
  • David, G., Barrett, E.F., Stimulation-evoked increases in cytosolic [Ca(2+)] in mouse motor nerve terminals are limited by mitochondrial uptake and are temperature-dependent (2000) J Neurosci, 20, pp. 7290-7296
  • 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
  • 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 (Berl), 107, pp. 35-46
  • Santafe, M.M., Urbano, F.J., Lanuza, M.A., Uchitel, O.D., Multiple types of calcium channels mediate transmitter release during functional recovery of botulinum toxin type A-poisoned mouse motor nerve terminals (2000) Neuroscience, 95, pp. 227-234
  • 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
  • Dasgupta, A., Simpson, J.A., Relation between firing frequency of motor units and muscle tension in the human (1962) Electromyography, 2, pp. 117-128
  • Brooks, B.R., Shodis, K.A., Lewis, D.H., Rawling, J.D., Sanjak, M., Belden, D.S., Natural history of amyotrophic lateral sclerosis. Quantification of symptoms, signs, strength, and function (1995) Adv Neurol, 68, pp. 163-184
  • 6|. Mitchell JD. Amyotrophic lateral sclerosis: toxins and environment. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1: 235-50; 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
  • Piazza, O., Siren, A.L., Ehrenreich, H., Soccer, neurotrauma and amyotrophic lateral sclerosis: Is there a connection? (2004) Curr Med Res Opin, 20, pp. 505-508
  • Haley, R.W., Excess incidence of ALS in young Gulf War veterans (2003) Neurology, 61, pp. 750-756

Citas:

---------- APA ----------
Pagani, M.R., Reisin, R.C. & Uchitel, O.D. (2007) . Mechanisms of synaptic alteration mediated by antibodies from patients with amyotrophic lateral sclerosis . Revista Neurologica Argentina, 32(1), 9-19.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03250938_v32_n1_p9_Pagani [ ]
---------- CHICAGO ----------
Pagani, M.R., Reisin, R.C., Uchitel, O.D. "Mechanisms of synaptic alteration mediated by antibodies from patients with amyotrophic lateral sclerosis " . Revista Neurologica Argentina 32, no. 1 (2007) : 9-19.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03250938_v32_n1_p9_Pagani [ ]
---------- MLA ----------
Pagani, M.R., Reisin, R.C., Uchitel, O.D. "Mechanisms of synaptic alteration mediated by antibodies from patients with amyotrophic lateral sclerosis " . Revista Neurologica Argentina, vol. 32, no. 1, 2007, pp. 9-19.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03250938_v32_n1_p9_Pagani [ ]
---------- VANCOUVER ----------
Pagani, M.R., Reisin, R.C., Uchitel, O.D. Mechanisms of synaptic alteration mediated by antibodies from patients with amyotrophic lateral sclerosis . Rev. Neurol. Argent. 2007;32(1):9-19.
Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03250938_v32_n1_p9_Pagani [ ]