Anti-ganglioside Antibodies Present in Serum of Patients with Multiple Sclerosis and of Immunized with Gangliosides Rabbits Alter Neuronal Electrical Characteristics. Oleg Sotnikov, Emilia Zaprianova, Svetlana Sergeeva, Denislava Deleva, Andon Filchev, B. Sultanov, T. Krasnova

Abstract. Multiple sclerosis (MS) is considered to be the prototype of primary demyelination. However, imaging and morphological studies of recent years have challenged this view. There is new evidence that the neurons themselves are target in the disease process. On the other hand, a significant increase of some neuronal gangliosides and of anti- ganglioside antibodies (AgA) was detected in the serum of MS patients during the first attacks of the disease. In order to obtain more information concerning the effect of AgA on the neuronal electrogenesis we used sera of MS patients and of immunized with gangliosides rabbits, containing AgA. The studies were performed on the Retzius neuron of the leech. The frequency of the spontaneous activity, the amplitude and the duration of the spontaneous action potential, the threshold, the latency period and the reaction to the synaptic stimulation were determined. There was an increase of the threshold and the latency period after incubation in human and rabbit sera. The neuron generated double spontaneous impulses. The disturbance of the processes of habituation and sensitization was quite similar. The control sera had no effect on the neuronal electrogenesis. These findings give us ground to assume that AgA play a role in the alteration of neuronal electric characteristics. They further support the new concept of MS as a neuronal disease.

Keywords. Neuronal electrogenesis, anti-ganglioside antibodies, serum, multiple sclerosis.

References.

1. Ando S.: Gangliosides in the nervous system. Neurochem Int, 5: 507-537, 1983.

2. Christova-Grekova M., Svetoslavova M., Zaprianova E., Kadijsky D., Dikov A.: Effect of exogenic brain gangliosides on the CNS- clinical and immunological data. CR Acad Sci Bulg, 41: 145-147, 1988.

3. Christova-Grekova M., Svetoslavova M., Zaprianova E., Kadijsky D., Dikov A.: Effect of exogenic brain gangliosides on the CNS- morphological data. CR Acad Sci Bulg, 42: 131-134, 1989.

4. Cohen O., Sela Ben-Ami., Schwarts M., Eshhar N., Cohen I.: Multiple sclerosis-like disease induced in rabbits by immunization with brain gangliosides. Isr J. Med, 17: 711-714, 1981.

5. De Stefano N., Narayanan S., Francis G.S., Arnaoutelis R., Tartaglia M.C., Antel J.P., Matthews P.M., Arnоld D.L: Evidenсе of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neuro, 58: 65-70, 2001.

6. Ferguson B., Matyszak M.K., Esiri M.M., Perry V.H.: Axonal damage in acute multiple sclerosis lesions. Brain, 120: 393-399; 1997.

7. Gadea M., Martinezbisbal L., Espert R., Casanova B., Coret F., Celda B.: Spectroscopic axonal damage of the right locus coeruleus relates to selective attention impairment in early stage of relapsing-remitting multiple sclerosis. Brain, 127: 89-98, 2004.

8. Hadjiconstantinou M., Neff N.: GM1 ganglioside: in vitro trophic actions on central neurotransmitter systems. J Neurochem, 70: 1335-1345, 1998.

9. Howard L., Weiner M.: Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch Neuro, 61: 1613-1615, 2004.

10. Ilinov P., Kazarova E., Dimon Sv., Zaprianova E.: Direct thin-layer chromatographic method for isolation of gangliosides. J Liquid Chromatog, 13(10): 1921-1931, 1990.

11. Kuhlmann T., Lingfeld G., Bitsch A., Schuchardt J., Bruck W.: Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain, 125: 2202-2212, 2002.

12. Lagutenko UP.: Structural organization of the body brain of annelids (evolutionary and neuromorphological analysis). Leningrad ,Nauka, 1981.

13. Ledeen RW., Wu G.: Ganglioside function in the neuron. Trends Glycosci Glycotechn., 4: 174-187; 1992.

14. Mizutamari R., Wiegandt H., Nores G.: Characterization of anti-ganglioside antibodies present in normal human plasma. J Neuroimmunol, 50:215-220, 1994.

15. Poser C.M., Paty D.W., Scheingberg L., McDonald? W.I., Pavis I.A., Ebers G.C., Sibly W., Silberg D., Touertellotte W.: New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol, 13: 227-231, 1983.

16. Rapport M., Graf L., Huang Y., Brunner W., Yu R.: Antibodies to total brain gangliosides: titer and specifity of antisera. In: Svennerholm, Mandel, Dreyfus, Urban, eds. Structure and function of gangliosides. New York, Plenum Press, 327-334, 1980.

17. Sergeeva S.S.: Changes in the impulse activity of Retzius neuron in the leech during synaptic activation at different frequencies. Zh Vyssh Nerv Deiat Im IP Pavlova, 44(6): 1144-1147, 1994.

18. Sergeeva S.S.: The electrophysiological investigation of the topografy of the axo-dendrite synapses of the Retzius neuron of the leech. Sechenov Physiol J, 81( 10): 113-116, 1995.

19. Sergeeva S.S., Antipov A.D., Kamenev O.U.: The determination of the contents of the sialic acid in the nervous system of Hirudo meditinalis. In abctr IV Intern Conf "Kolosov reading-2002", St-Petersburg, RAN, 260, 2002.

20. Sergeeva S.S., Zaprianova E., Sotnikov O.S., Deleva D., Filchev A.: Analysis of the effects of antibodies to gangliosides on the electrical activity of Retzius neurons in the leech and on the functional activity of influx sodium curent chanels. Neurosci and Bichav Physiol, 34(6): 576-585, 2004.

21. Stevens A., Weller M., Wietholter H.: CSF and serum ganglioside antibody patterns in MS. Acta Neurol Scand, 86: 485-489, 1992.

22. Svennerholm L.: Gangliosides - a new therapeutic agent against stroke and Alzheimer's disease. Life Sciences, 55: 2125-2134, 1994.

23. Trapp B.D., Peterson J., Ransohoff R.M., Rudick R., Mork S., Bo L.: Axonal transection in the lesions of multiple sclerosis. N Engl J Med, 338(5): 278-285, 1998.

24. Vingerchuk M., Luccinetti C., Noseworthy J.: Biology of disease. Multiple sclerosis: current pathological concepts. Lab Inves,t 81 (3): 263-281, 2001.

25. Waxman S.: Multiple sclerosis as a neuronal disease. Arch Neurol, 57: 22-24, 2000.

26. Wiegandt H.: Gangliosides: Structure and physiological possibility. Brain Res, 66: 85-97, 1995.

27. Yong V.: Prospects for neuroprotection in multiple sclerosis. Frontiers in Bioscience, 9: 864-872, 2004.

28. Zaprianova E., Deleva D., Hauttecoeur B., Bakalska M., Filchev A : Ganglioside spinal cord changes in chronic relapsing experimental allergic encephalomyelitis induced in the Lewis rats. Neurochem Res, 22 (2): 175-179, 1997.

29. Zaprianova E., Deleva D., Ilinov P., Filchev A.: Ganglioside brain changes in chronic relapsing experimental allergic encephalomyelitis induced in the Lewis rats. Neurochem Research, 23 (11): 1421-1425, 1998.

30. Zaprianova E., Deleva D., Ilinov P., Sultanov E., Filchev A., Christova L., Sultanov B.: Serum ganglioside patterns in multiple sclerosis. Neurochem Res, 2: 95-100, 2001.

31. Zaprianova E., Deleva D., Majtenyi K., Sultanov E., Filchev A., Sultanov B., Kolyovska V.: Serum GD1a ganglioside in patients with multiple sclerosis. Acta morphol et anthropol, 8: 3-7, 2003.

32. Zaprianova E., Deleva D., Filchev A.: GD1a ganglioside spinal cord changes in chronic relapsing experimental allergic encephalomyelitis induced in the Lewis rats. Acta morphol et anthropol, 9: 3-8, 2004.

33. Zaprianova E., Sotnikov O.S., Sergeeva S.S., Deleva D., Filchev A., Sultanov B.: Axon reactions precede demyelination in experimental models of multiple sclerosis. Neurosci and Bihav Physiol, 34(4): 337-342, 2004.

34. Zaprianova E., Majtenyi K., Deleva D., Mikova O., Filchev A., Sultanov B., Kolyovska V., Sultanov E., Christova L., Kmetska X., Georgiev D.: Serum IgG and IgM ganglioside GM1 antibodies in patients with multiple sclerosis. Clin Neurosc, 57( 3-4): 94-99, 2004.