Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-23T08:28:58.621Z Has data issue: false hasContentIssue false

A murine model for cerebral toxocariasis: characterization of host susceptibility and behaviour

Published online by Cambridge University Press:  14 February 2006

C. M. HAMILTON
Affiliation:
Parasitology Research Group, School of Natural Sciences, Department of Zoology, University of Dublin, Trinity College, Dublin 2, Ireland
P. STAFFORD
Affiliation:
Parasitology Research Group, School of Natural Sciences, Department of Zoology, University of Dublin, Trinity College, Dublin 2, Ireland
E. PINELLI
Affiliation:
Department of Parasitology and Mycology, Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands
C. V. HOLLAND
Affiliation:
Parasitology Research Group, School of Natural Sciences, Department of Zoology, University of Dublin, Trinity College, Dublin 2, Ireland

Abstract

Toxocara canis, the parasitic roundworm of dogs, can infect a number of paratenic hosts, such as mice and humans, due to the widespread dissemination of its ova in the environment. In these paratenic hosts, larvae have been shown to exhibit a predilection for the central nervous system, resulting in an increasing number of parasites migrating to the brain as infection progresses. In an initial experiment, we investigated the differential brain involvement of T. canis in 7 strains of inbred mice, and chose 2 strains, susceptible (BALB/c) and resistant (NIH) to cerebral infection. In a second experiment, both strains were investigated in terms of course of migration, larval accumulation, and behavioural response to T. canis infection. Results revealed that infected BALB/c mice took significantly longer to drink from a water source (following a period of deprivation), compared with control mice, indicating some degree of memory impairment. Cerebral larval recoveries from both strains of mice demonstrated variation between the two experiments, suggesting that larval burdens may not be a reliable indicator of susceptibility or resistance to T. canis infection. The percentage of total recovered larvae in each organ may be a better representation of larval distribution. Our model system may provide insights into the impact of chronic geohelminth infection on cognitive development.

Type
Research Article
Copyright
2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Abo-Shehada, M. N. and Herbert, I. V. ( 1989). Variations in innate resistance to experimental Toxocara canis infection in two strains of mice. Veterinary Parasitology 33, 297307.CrossRefGoogle Scholar
Alizadeh, H. and Wakelin, D. ( 1983). Genetic factors controlling the intestinal mast cell response in mice infected with Trichinella spiralis. Clinical and Experimental Immunology 49, 331337.Google Scholar
Bardon, R., Cuellar, C. and Guillen, J. L. ( 1994). Larval distribution of Toxocara canis in BALB/c mice at nine weeks and one year post-inoculation. Journal of Helminthology 68, 359360.CrossRefGoogle Scholar
Beaver, P. C., Synder, C. H., Carerra, G. M., Dent, J. H. and Lafferty, J. W. ( 1952). Chronic eosinophilia due to visceral larva migrans. Pediatrics 9, 7.Google Scholar
Beck, J. A., Lloyd, S., Hafezparast, M., Lennon-Pierce, M., Eppig, J. T., Festing, M. F. W. and Fisher, E. M. C. ( 2000). Genealogies of mouse inbred strains. Nature Genetics 24, 2325.CrossRefGoogle Scholar
Brown, H., Turner, G., Rogerson, S., Tembo, M., Mwenechanya, J., Molyneux, M. and Taylor, T. ( 1999). Cytokine expression in the brain in human cerebral malaria. Journal of Infectious Diseases 180, 17421746.CrossRefGoogle Scholar
Burren, C. H. ( 1971). The distribution of Toxocara canis larvae in the central nervous system of the mouse. Transactions of the Royal Society of Tropical Medicine and Hygiene 65, 450453.CrossRefGoogle Scholar
Burright, R. G., Donovick, P. J., Dolinsky, Z., Hurd, Y. and Cypess, R. ( 1982). Behavioural changes in mice infected with Toxocara canis. Journal of Toxicology and Environmental Health 10, 621626.CrossRefGoogle Scholar
Cox, D. M. ( 1996). The effect of Toxocara canis infection on the paratenic host behaviour of two strains of mice. Unpublished Ph.D. thesis, University of Dublin.
Cox, D. and Holland, C. V. ( 1998). The relationship between numbers of larvae recovered from the brain of Toxocara canis-infected mice, and social behaviour and anxiety in the host. Parasitology 116, 579594.CrossRefGoogle Scholar
Cox, D. and Holland, C. V. ( 2001 a). Influence of mouse strain, infective dose and larval burden in the brain on activity in Toxocara-infected mice. Journal of Helminthology 75, 2332.Google Scholar
Cox, D. and Holland, C. V. ( 2001 b). Relationship between three intensity levels of Toxocara canis larvae in the brain, and effects on exploration, anxiety, learning and memory in the murine host. Journal of Helminthology 75, 3341.Google Scholar
Dehlawi, M. S. and Goyal, P. K. ( 2003). Responses of inbred mice strains to infection with intestinal nematodes. Journal of Helminthology 77, 119124.CrossRefGoogle Scholar
Del Prete, G. F., De Carli, M., Mastromauro, C., Biagiotti, R., Macchia, D., Falagiani, P., Ricci, M. and Romagnani, S. ( 1991). Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. Journal of Clinical Investigation 88, 346350.CrossRefGoogle Scholar
Dolinksy, Z. S., Burright, R. G. and Donovick, P. J. ( 1981). Behavioural effects of lead and Toxocara canis in mice. Science 213, 11421144.Google Scholar
Dubinsky, P., Havasiova-Reiterova, K., Petko, B., Hovorka, I. and Tomasovicova, O. ( 1995). Role of small mammals in the epidemiology of toxocariasis. Parasitology 110, 187193.CrossRefGoogle Scholar
Dunsmore, J. D., Thompson, R. C. A. and Bates, I. A. ( 1983). The accumulation of Toxocara canis larvae in the brains of mice. International Journal for Parasitology 13, 517521.CrossRefGoogle Scholar
Epe, C., Sabel, T., Schnieder, T. and Stoye, M. ( 1994). The behaviour and pathogenicity of Toxocara canis larvae in mice of different strains. Parasitology Research 80, 691695.CrossRefGoogle Scholar
Festing, M. F. W. and Fisher, E. M. C. ( 2000). Mighty mice. Nature, London 404, 815.CrossRefGoogle Scholar
Flanagan, A. ( 2005). A murine model for cerebral toxocariasis: contribution of host genotype and infection duration on learning and memory. Unpublished Moderatorship Thesis, University of Dublin.
Gazzinelli, R. T., Eltoum, I., Wynn, T. A. and Sher, A. ( 1993). Acute cerebral toxoplasmosis is induced by in vivo neutralisation of TNF-α and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. Journal of Immunology 151, 36723681.Google Scholar
Glickman, L. T., Cypress, R., Crumrine, P. K. and Gitlin, D. A. ( 1979). Toxocara infection and epilepsy in children. Journal of Pediatrics 94, 7578.CrossRefGoogle Scholar
Good, B. ( 1998). Epidemiological and experimental aspects of Toxocara infection in humans and mice. Unpublished Ph.D. thesis, University of Dublin.
Good, B., Holland, C. V. and Stafford, P. ( 2001). The influence of inoculum size and time post-infection on the number and position of Toxocara canis larvae recovered from the brains of outbred CD1 mice. Journal of Helminthology 75, 175181.Google Scholar
Hill, I. R., Denham, D. A. and Scholtz, C. L. ( 1985). Toxocara canis larvae in the brain of a British child. Transactions of the Royal Society of Tropical Medicine and Hygiene 79, 351354.CrossRefGoogle Scholar
Holland, C. V., O'Lorcain, P., Taylor, M. R. H. and Kelly, A. ( 1995). Sero-epidemiology of toxocariasis in school children. Parasitology 110, 535545.CrossRefGoogle Scholar
Holland, C. V. and Cox, D. ( 2001). Toxocara in the mouse: a model for parasite-altered host behaviour. Journal of Helminthology 75, 125135.Google Scholar
Holland, C. and Hamilton, C. ( 2005). The significance of cerebral toxocariasis. In Toxocara: the Enigmatic Parasite (ed. Holland, C. V. and Smith, H. V.), CABI Publishing, Wallingford, Oxon, UK (in the Press).
Hutchison, W. M., Bradley, M., Cheyne, W. M., Wells, B. W. P. and Hay, J. ( 1980). Behavioural abnormalities in Toxoplasma-infected mice. Annals of Tropical Medicine and Parasitology 74, 337345.CrossRefGoogle Scholar
Kaplan, M., Kalkan, A., Hosoglu, S., Kuk, S., Özden, M., Demirdag, K. and Ozdarendeli, A. ( 2004). The frequency of Toxocara infection in mental retarded children. Memorias do Instituto Oswaldo Cruz 99, 121125.CrossRefGoogle Scholar
Kavaliers, M. and Colwell, D. D. ( 1995). Reduced spatial learning in mice infected with the nematode, Heligmosomoides polygyrus. Parasitology 110, 591597.CrossRefGoogle Scholar
Kavaliers, M., Colwell, D. D. and Galea, L. A. M. ( 1995). Parasitic infection impairs spatial learning in mice. Animal Behaviour 50, 223229.CrossRefGoogle Scholar
Kershaw, W. E., Leytham, G. W. H. and Dickerson, G. ( 1959). The effect of schistosomiasis on animal intelligence. Annals of Tropical Medicine and Parasitology 53, 504506.CrossRefGoogle Scholar
Kuroda, E., Yoshida, Y., En Shan, B. and Yamashita, U. ( 2001). Suppression of macrophage interleukin-12 and tumour necrosis factor-alpha production in mice infected with Toxocara canis. Parasite Immunology 23, 305311.CrossRefGoogle Scholar
Lee, H. F. ( 1960). Effects of superinfection on the behaviour of Toxocara canis larvae in mice. Journal of Parasitology 46, 583588.CrossRefGoogle Scholar
Lee, T. D. G. and Wakelin, D. ( 1982). The use of host strain variation to assess the significance of mucosal mast cells in the spontaneous cure response of mice to the nematode Trichuris muris. International Archives of Allergy and Applied Immunology 67, 302305.CrossRefGoogle Scholar
Magnaval, J.-F., Galindo, V., Glickman, L. T. and Clanet, M. ( 1997). Human Toxocara infection of the central nervous system and neurological disorders: a case-control study. Parasitology 115, 537543.CrossRefGoogle Scholar
Marmor, M., Glickman, L., Shofer, F., Faich, L., Rosenberg, C., Cornblatt, B. and Friedman, S. ( 1987). Toxocara canis infection of children: Epidemiologic and neuropsychologic findings. American Journal of Public Health 77, 554559.CrossRefGoogle Scholar
Olson, L. J. and Rose, J. E. ( 1966). Effect of Toxocara canis infection on the ability of white rats to solve maze problems. Experimental Parasitology 19, 7784.CrossRefGoogle Scholar
Pritchard, M. H. and Kruse, G. O. W. ( 1982). The Collection and Preservation of Animal Parasites. University of Nebraska Press, Lincoln and London.
Restrepo, B. I., Llaguno, P., Sandoval, M. A., Enciso, J. A. and Teale, J. M. ( 1998). Analysis of immune lesions in neurocysticercosis patients: central nervous system response to helminth appears Th1-like instead of Th2. Journal of Neuroimmunology 89, 6472.CrossRefGoogle Scholar
Skerrett, H. and Holland, C. V. ( 1997). Variation in the larval recovery of Toxocara canis from the murine brain: implications for behavioural studies. Journal of Helminthology 71, 253255.CrossRefGoogle Scholar
Smith, H. V. ( 1991). Immune evasion and immunopathology in Toxocara canis infection. In Parasitic Nematodes – Antigens, Membranes and Genes ( ed. Kennedy, M. W.), pp. 117139. Taylor and Francis, London.
Sprent, J. F. A. ( 1955). On the invasion of the central nervous system by nematodes II. Invasion of the nervous system in Ascariasis. Parasitology 45, 4158.Google Scholar
Taylor, M. R. H., Keane, C. T., O'Connor, P., Girdwood, R. W. A. and Smith, H. ( 1987). Clinical features of covert toxocariasis. Scandinavian Journal of Infectious Diseases 19, 693696.CrossRefGoogle Scholar
Thomson, D. E., Bundy, D. A. P., Cooper, E. S. and Schantz, P. M. ( 1986). Epidemiological characteristics of Toxocara canis zoonotic infection of children in a Caribbean community. Bulletin of the World Health Organization 64, 283290.Google Scholar
Wang, M. Q., Jiang, H. J., Inoue, H., Myozaki, M. and Yamashita, U. ( 1995). B cell mitogenic activity of Toxocara canis adult worm antigen. Parasite Immunology 17, 609615.CrossRefGoogle Scholar
Wilder, H. C. ( 1950). Nematode endophdalmitis. Transactions of the American Academy of Opthalmology and Otolaryngology 55, 99109.Google Scholar
Witting, P. A. ( 1979). Learning capacity and memory of normal and Toxoplasma-infected laboratory rats and mice. Zeitschrift für Parasitenkunde 61, 2951.CrossRefGoogle Scholar
Worley, G., Green, J. A., Frothingham, T. E., Sturner, R. A., Walls, K. W., Pakalnis, V. A. and Ellis, G. S. Jr. ( 1984). Toxocara canis infection: clinical and epidemiological associations with seropositivity in kindergarten children. Journal of Infectious Diseases 149, 591597.CrossRefGoogle Scholar