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Characterization of a GABAergic neurotransmission in adult Schistosoma mansoni

Published online by Cambridge University Press:  06 August 2004

D. L. MENDONÇA-SILVA ,
P. F. GARDINO ,
R. C. C. KUBRUSLY ,
F. G. DE MELLO  and
F. NOËL
D. L. MENDONÇA-SILVA
Affiliation:
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brazil
P. F. GARDINO
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brazil
R. C. C. KUBRUSLY
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brazil
F. G. DE MELLO
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brazil
F. NOËL
Affiliation:
Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590, Rio de Janeiro, Brazil
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Abstract

The neuromuscular systems of parasitic helminths are targets that are particularly amenable for anthelmintics. In this study, we describe a GABAergic neurotransmission in adult Schistosoma mansoni, the trematode responsible for high levels of morbidity in people living in developing countries. GABA immunoreactivity (GABA-IR) was detected in nerve cells and fibres of the cerebral ganglia and longitudinal nerve cords and the nerve plexuses ramifying throughout the parenchyma of male adult worms. In addition, strong GABA-IR was also found associated with the oral and ventral suckers as well as in testes indicating a role for GABA in fixation to the host vascular wall and spermatogenesis. The capacity to synthesize GABA from glutamate was confirmed by measurement of a glutamate decarboxylase (GAD) activity. Supporting these data, a single band with an apparent molecular weight of about 67 kDa was detected using an antibody raised against mammalian GAD. In vivo studies revealed that picrotoxin, a non-competitive antagonist of the GABAA receptor, produced a modification of the motility and locomotory behaviour of adult worms, suggesting that GABAergic signalling pathway may play a physiological role in the motonervous system of S. mansoni and could be considered as a potential target for the development of new drugs.

Keywords

Schistosoma mansonihelminthsGABAglutamate decarboxylasenervous systemneurotransmissionimmunohistochemistry
Type
Research Article
Information
Parasitology , Volume 129 , Issue 2 , August 2004 , pp. 137 - 146
Copyright
2004 Cambridge University Press

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References

REFERENCES

BAO, J., CHEUNG, W. Y. & WU, J-Y. (1995). Brain L-glutamate decarboxylase inhibition by phosphorylation and activation by dephosphorylation. Journal of Biological Chemistry 270, 6464–6467.CrossRefGoogle Scholar
BRADFORD, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle Scholar
BROWNLEE, D. J. A. & FAIRWEATHER, I. (1999). Exploring the neurotransmitter labyrinth in nematodes. Trends in Neurosciences 22, 16–24.CrossRefGoogle Scholar
CALOGERO, A. E., HALL, J., FISHEL, S., GREEN, S., HUNTER, A. & D'AGATA, R. (1996). Effects of gamma-aminobutyric acid on human sperm motility and hyperactivation. Molecular Human Reproduction 2, 733–738.CrossRefGoogle Scholar
CUNHA, V. M. N., MEVER-FERNANDES, J. R. & NOËL, F. (1992). A (Ca2+–Mg2+) ATPase from Schistosoma mansoni is coupled to an active transport of calcium. Molecular and Biochemical Parasitology 52, 167–174.CrossRefGoogle Scholar
DAY, T. A., BENNETT, J. L. & PAX, R. A. (1994). Serotonin and its requirement for maintenance of contractility in muscle fibres isolated from Schistosoma mansoni. Parasitology 108, 425–432.CrossRefGoogle Scholar
DE MELLO, F. G., BACHRACH, U. & NIRENBER, G. M. (1976). Ornithine and glutamic acid decarboxylase activities in the developing chick retina. Journal of Neurochemistry 27, 847–851.CrossRefGoogle Scholar
ERIKSSON, K. S. & PANULA, P. (1994). Gamma-aminobutyric acid in the nervous system of a planarian. The Journal of Comparative Neurology 345, 528–536.CrossRefGoogle Scholar
ERIKSSON, K. S., MAULE, A. G., HALTON, D. W., PANULA, P. A. J. & SHAW, C. (1995). GABA in the nervous system of parasitic flatworms. Parasitology 110, 339–346.CrossRefGoogle Scholar
ERLANDER, M. G., TILLAKARATNE, N. J. K., FELDBLUM, S., PATEL, N. & TOBIN, A. J. (1991). Two genes encode distinct glutamate decarboxylases. Neuron 7, 91–100.CrossRefGoogle Scholar
FENWICK, A., SAVIOLI, L., ENGELS, D., BERGQUIST, N. R. & TODD, M. H. (2003). Drugs for the control of parasitic diseases: current status and development in schistosomiasis. Trends in Parasitology 19, 509–515.CrossRefGoogle Scholar
GUSTAFSSON, M. K. S. (1987). Immunocytochemical demonstration of neuropeptides and serotonin in the nervous system of adult Schistosoma mansoni. Parasitology Research 74, 168–174.CrossRefGoogle Scholar
KEENAN, L., KOOPOWITS, H. & BERNARDO, K. (1979). Primitive nervous system. Action of aminergic drugs and blocking agents on activity in the ventral nerve cord of the flatworm Notoplana acticola. Journal of Neurobiology 10, 397–408.Google Scholar
HALTON, D. W. & GUSTAFSSON, M. K. S. (1996). Functional morphology of the platyhelminth nervous system. Parasitology 113, S47–S72.CrossRefGoogle Scholar
HOLDEN-DYE, L., KROGSGAARD-LARSEN, P., NIELSEN, L. & WALKER, R. J. (1989). GABA receptors on the somatic muscle cells of the parasitic nematode Ascaris suum: stereoselectivity indicates similarity to a GABAA-type agonist recognition site. British Journal of Pharmacology 98, 841–850.CrossRefGoogle Scholar
JIN, Y., JORGENSEN, E., HARTWIEG, E. & HORVITZ, H. R. (1999). The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development. The Journal of Neuroscience 19, 539–548.Google Scholar
JOHNSON, C. D. & STRETTON, A. O. W. (1987). GABA-like immunoreactivity in inhibitory motor neurons of the nematode Ascaris. Journal of Neuroscience 7, 223–235.CrossRefGoogle Scholar
LAEMMLI, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227, 680–685.CrossRefGoogle Scholar
MACHADO-SILVA, J. R., PELAJO-MACHADO, M., LENZI, H. L. & GOMES, D. C. (1998). Morphological study of adult male worms of Schistosoma mansoni sambon, 1907 by confocal laser scanning microscopy. Memórias do Instituto Oswaldo Cruz 93, 303–307.CrossRefGoogle Scholar
MAIR, G. R., MAULE, A. G., DAY, T. A. & HALTON, D. W. (2000). A confocal microscopical study of the musculature of adult Schistosoma mansoni. Parasitology 121, 163–170.CrossRefGoogle Scholar
MARTIN, R. J. (1987). The γ-aminobutyric acid of Ascaris as a target for anthelmintics. Biochemical Society Transactions 17 61–65.CrossRefGoogle Scholar
McINTIRE, S. L., JORGENSEN, E., KAPLAN, J. & HORVITZ, H. R. (1993). The GABAergic nervous system of Caenorhabditis elegans. Nature, London 364, 337–341.CrossRefGoogle Scholar
MELLIN, T., BUSCH, R., WANG, C. & KATH, G. (1983). Neuropharmacology of the parasitic trematode Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene 32, 83–93.CrossRefGoogle Scholar
MENDONÇA-SILVA, D. L., PESSÔA, R. F. & NOËL, F. (2002). Evidence for the presence of glutamatergic receptors in adult Schistosoma mansoni. Biochemical Pharmacology 64, 1337–1344.CrossRefGoogle Scholar
NOËL, F., CUNHA, V. M. N., SILVA, C. L. M. & MENDONÇA-SILVA, D. L. (2001). Control of calcium homeostasis in Schistosoma mansoni. Memórias do Instituto Oswaldo Cruz 96 (Supp.), 85–88.CrossRefGoogle Scholar
OERTEL, W. H., SCHMECHEL, D. E., TAPPAZ, M. L. & KOPIN, I. J. (1981). Production of a specific antiserum to rat brain glutamic acid decarboxylase by injection of an antigen-antibody complex. Neuroscience 6, 2689–2700.CrossRefGoogle Scholar
PAX, R. A. & BENNETT, J. L. (1992). Neurobiology of parasitic flatworms: How much “neuro” in the biology? Journal of Parasitology 78, 194–205.Google Scholar
PHILLIPS, A. M., SALKOFF, L. B. & KELLY, L. E. (1993). A neural gene from Drosophila melanogaster with homology to vertebrate and invertebrate glutamate decarboxylases. Journal of Neurochemistry 61, 1291–1301.CrossRefGoogle Scholar
RAYMOND, V. & SATTELLE, D. B. (2002). Novel animal-health drug targets from ligand-gated chloride channels. Nature Reviews Drug Discovery 1, 427–436.CrossRefGoogle Scholar
REMME, J. H., BLAS, E., CHITSULO, L., DESJEUX, P. M., ENGERS, H. D., KANYOK, T. P., KENGEYA KAYONDO, J. F., KIOY, D. W., KUMARASWAMI, V., LAZDINS, J. K., NUNN, P. P., ODUOLA, A., RIDLEY, R. G., TOURE, Y. T., ZICKER, F. & MOREL, C. M. (2002). Strategic emphases for tropical diseases research: a TDR perspective. Trends in Parasitoligy 18, 421–426.CrossRefGoogle Scholar
RITTA, M. N., CALAMERA, J. C. & BAS, D. E. (1998). Occurrence of GABA and GABA receptors in human spermatozoa. Molecular Human Reproduction 4, 769–773.CrossRefGoogle Scholar
SHI, Q. X., YUAN, Y. Y. & ROLDAN, E. R. (1997). γ-aminobutyric acid (GABA) induces the acrosome reaction in human spermatozoa. Molecular Human Reproduction 3, 677–683.CrossRefGoogle Scholar
SILK, M. H. & SPENCE, I. M. (1969). Ultrastructural studies of the blood fluke – Schistosoma mansoni. II. The musculature. South African Journal of Medical Science 34, 11–20.Google Scholar
SIMPSON, A. J. G., SINGER, D., McCUTCHAN, T. F., SACKS, D. L. & SHER, A. (1983). Evidence that schistosome MHC antigens are not synthesized by the parasite but are acquired from the host in intact glycoproteins. Journal of Immunology 131, 962–965.Google Scholar
SMITHERS, S. R. & DOENHOFF, M. J. (1982). Schistosomiasis. In Immunology of Parasitic Diseases ( ed. Cohen, S. & Warren, K. S.), pp. 527–607. Blackwell Scientific, Oxford, UK.
SOLIS-SOTO, J. M. & BRINK, M. D. J. (1994). Immunocytochemical study on biologically active neurosubstances in daughter sporocysts and cercariae of Trichobilharzia ocellata and Schistosoma mansoni. Parasitology 108, 301–311.CrossRefGoogle Scholar
TILLAKARATNE, N. J., ERLANDER, M. G., COLLARD, M. W., GREIF, K. F. & TOBIN, A. J. (1992). Glutamate decarboxylases in nonneural cells of rat testis and oviduct: differential expression of GAD65 and GAD 67. Journal of Neurochemistry 58, 618–627.CrossRefGoogle Scholar
VERJOVSKI-ALMEIDA, S., DEMARCO, R., MARTINS, E. A. L., GUIMARÃES, P. E. M., OJOPI, E. P. B., PAQUOLA, A. C. M., PIAZZA, J. P., NISHIYAMA Jr., M. Y., KITAJIMA, J. P., ADAMSON, R. E., ASHTON, P. D., BONALDO, M. F., COULSON, P. S., DILLON, G. P., FARIAS, L. P., GREGORIO, S. P., HO, P. L., LEITE, R. A., MALAQUIAS, L. C. C., MARQUES, R. C. P., MIYASATO, P. A., NASCIMENTO, A. L. T. O., OHLWEILER, F. P., REIS, E. M., RIBEIRO, M. A., SÁ, R. G., STUKART, G. C., SOARES, M. B., GARGIONI, C., KAWANO, T., RODRIGUES, V., MADEIRA, A. M. B. N., WILSON, R. A., MENCK, C. F. M., SETUBAL, J. C., LEITE, L. C. C. & DIAS-NETO, E. (2003). Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni. Nature Genetics 35, 148–157.CrossRefGoogle Scholar
WALKER, R. J. & HOLDEN-DYE, L. (1991). Evolutionary aspects of transmitter molecules, their receptors and channels. Parasitology 102, S27–S29.CrossRefGoogle Scholar