Skip to main content
Download PDF

Neurotoxic Effects of Prenatal Trichlorfon Administration in Pigs

Nevrotoksiske effekter forårsaket av prenatal administrasjon av triklorfon til gris

Acta Veterinaria Scandinavica volume 28, pages 321–332 (1987)Cite this article

Abstract

Pregnant sows were administered trichlorfon (Neguvon®) during gestation. Examination of the offspring revealed clinical symptoms which included ataxia and tremor. The weights of the cerebrum and the celebellum were significantly reduced (67% and 41% of the control values). There was a clear correlation between the decrease in total brain weight and decrease in cerebellar weight (r = 0.94). Histological examination showed a well preserved lamination of the cerebral and cerebellar cortex. Periodical loss of Purkinje cells was the most notable finding in the cerebellum. The molecular layer in such regions was markedly thinned. Neurochemical investigations of the cerebellum showed a significant decrease in specific activity of the transmitter synthesizing enzymes choline acetyltransferase, glutamate decarboxylase and aromatic amino acid decarboxylase (61.6%, 30.3% and 47.1% of the control values, respectively). No effect in high affinity D-aspartate uptake was observed.

Sammendrag

Drektive purker ble gitt triklorfon (Neguvon®) oralt på dag 71, 77, 87 og 98 etter bedekning. Grisungene viste symptomer som ataksi og tremor. Vektene av cerebrum og cerebellum var signifikant redusert og utgjorde henholdsvis 67% og 41% av kontrolldyrene. Det var klar korrelasjon mellom reduksjonen i total hjernevekt og reduksjonen i vekten av cerebellum (r = 0.94). Histologiske undersøkelser viste en tydelig laminering av cortex både i cerebrum og cerebellum. Stedvis tap av Purkinje celler ble observert i cerebellum.

Nevrokjemiske undersøkelser av cerebellum viste signifikant reduksjon i aktiviteten av de transmittor syntetiserende enzymene kolin acetyltransferase, glutamat dekarboksylase og aromatisk aminosyre dekarboksylase (henholdsvis 30,4%, 69,7% og 52,9% av kontrollverdiene). Ingen effekt på høy affinitet D-aspartat opptak ble observert.

References

  • Albers R W, Brady R O: The distribution of glutamate decarboxylase in the nervous system of the rhesus monkey. J. Biol. Chem. 1959,234, 926–928.

    Article  CAS  PubMed  Google Scholar 

  • Baron R L, Johnson H: Neurological disruption produced in hens by two organophosphate esters. Brit. J. Pharmacol. 1964,23, 295–304.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Berge G Ν, Nafstad I: Teratogenicity and embryoto-xicity of orally administered fenchlorphos in blue foxes. Acta vet. scand. 1983,24, 99–112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Black I R: Regulation of autonomic development. Annu. Rev. Neurosci. 1978,1, 183–214.

    Article  CAS  PubMed  Google Scholar 

  • Broch O J, Fonnum F: The regional and subcellular distribution of catechol-O-methyl-transferase in the rat brain. J. Neurochem. 1972,19, 2049–2055.

    Article  CAS  PubMed  Google Scholar 

  • Budreau C H, Singh R P: Teratogenicity and em-bryotoxicity of demeton and fenthion in CF # 1 mouse embryos. Toxicol. Appi. Pharmacol. 1973,24, 324–332.

    Article  CAS  Google Scholar 

  • Bunge R, Johnson M, Ross CD: Nature and narture in development of the autonomic neuron. Science 1978,199, 1409–1416.

    Article  CAS  PubMed  Google Scholar 

  • Byron J W: Manipulation of the cell cycle of the hemopoietic stem cell. Exp. Hematol. 1975,3, 44–53.

    CAS  PubMed  Google Scholar 

  • Belske G, Kronevi T, Lindgren Ν O: Congenital tremor in pigs in Sweden. Nord. Vet. Med. 1978,30, 534–537.

    Google Scholar 

  • Davison A N, Dobbing J: Myelination as a vulnerable period in brain development. Brit. Med. Bull. 1966,22, 40–44.

    Article  CAS  PubMed  Google Scholar 

  • Dickerson JWT, Dobbing J: Prenatal and postnatal growth and development of the central nervous system of the pig. Proc. Roy. Soc. B. 1967,166, 384–395.

    CAS  Google Scholar 

  • Dobbing J: Vulnerable periods of brain development. In: CIBA Foundation Symposia. Lipids, Malnutrition & the Developing Brain. Elsevier, Amsterdam 1972, p. 9–20.

    Google Scholar 

  • Done J T, Hebert N: The growth of the cerebellum in the foetal pig. Res. Vet. Sci. 1968,9, 143–148.

    Article  CAS  PubMed  Google Scholar 

  • Fatzer R, Hani H, Scholl E: Ko.igenitaler Tremor und zerebelläre Hypoplasie bei Ferkeln nach Be-handlung der Mutterschweine mit Neguvon® wáhrend der Trächtigkeit. (Congenital tremor and cerebellar hypoplasia in piglets following trichlorfon treatment of pregnant sows). Schweiz. Arc. Tierheil. 1981 12, 29–36.

    Google Scholar 

  • Fonnum F: Localization of cholinergic and y-amino-butyric acid containing pathways in brain. In: Metabolic Compartmentation in the Brain, ed. R. Balázs and J. E. Cremer. The Macmillan Press Ltd. 1972, p. 245–257.

    Google Scholar 

  • Fonnum F: A rapid radiochemical method for the determination of choline acetyltransferase. J. Neurochem. 1975, 25, 407–409.

    Article  Google Scholar 

  • Fonnum F, Walaas I, Iversen E: Localization of GA-BAergic, cholinergic and aminergic structures on the mesolimbic system. J. Neurochem. 1977,29, 221–230.

    Article  CAS  PubMed  Google Scholar 

  • Fonnum F, Storm-Mathisen J, Divac I: Biochemical evidence for glutamate as neurotransmitter in corticostriatal and corticothalamic fibres in rat brain. Neuroscience 1981,6, 863–873.

    Article  CAS  PubMed  Google Scholar 

  • Gamlem HN, Lund A, Moen J H, Berge G Ν: Kongenital tremor og cerebellum-hypoplasi hos sped-griser som en mulig folge av Neguvon®-behand-ling av drektige purker. (Congenital tremor and cerebellar hypoplasia in piglets associated with trichlorfon-treatment of pregnant sows). II. En kasuistisk meddelelse. Norsk Vet. tidssk. 1983,6, 385–387.

    Google Scholar 

  • Greenberg J, La Ham Q N: Malathion induced tera-tism in the developing chick. Can. J. Zool. 1969,47, 539–542.

    Article  CAS  PubMed  Google Scholar 

  • Harbison R D, Olubadewo J, Dmvedi C, Sastry Β V R: Proposed role of the placental cholinergic system in the regulation of fetal growth and development. In: Basic and Therapeutic Aspects of Perinatal Pharmacology, ed. P. L. Morselli, S. Garattini and F. Sereni, Raven Press, New York, 1975, p. 107–120.

    Google Scholar 

  • Harding JDJ, Done J T, Darbyshire J H: Congeni-tal tremor in piglets and their relation to swine fever. Vet. Ree. 1966,79, 388–389.

    Article  CAS  Google Scholar 

  • Kàsa Ρ, Silver A: The correlation between choline acetyltransferase and acetylcholinesterase activity in different areas of the cerebellum of rat and guinea pig. J. Neurochem. 1969,16, 389–396.

    Article  Google Scholar 

  • Khera Κ S: Toxic and teratogenic effects of insecticides in duck and chick embryos. Toxicol. Appi. Pharmacol. 1966, 8, 345.

    Article  Google Scholar 

  • Khera Κ S, La Ham Q Ν, Ellis C F, Zawidzka Ζ Ζ, Grice C H: Foot deformity in duck from injection of EPN during embryogenesis. Toxicol. Appi. Pharmacol. 1967,8, 540–549.

    Article  Google Scholar 

  • Kimbrough R D, Gaines Τ Β: Effect on organic phosphorus compounds and alkylating agents on the rat fetus. Arch. Environ. Health 1968,16, 805–808.

    Article  CAS  PubMed  Google Scholar 

  • Knox B, Askaa J, Basse A, Bitsch V, Eskildsen M, Mandrup M, Ottosen ΗE, Overby E, Pedersen K B, Rasmussen F: Congenital ataxia and tremor with cerebellar hypoplasia in piglets born by sows treated with Neguvon® vet. during pregnancy. Nord. Vet. Med. 1978,30, 538–545.

    CAS  PubMed  Google Scholar 

  • Kronevi T: Kan Neguvon®-behandling av dràktiga suggor orsaka cerebellar hypoplasi hos gris? (Can Neguvon®-treatment of pregnant sows cause cerebellar hypoplasia in piglets?). Svensk Vet. tid. 1977,29, 931–932.

    Google Scholar 

  • Kronevi T, Bäckström L: Kongenital tremor (skak-sjuke) hos gris (Congenital tremor in piglets). Svensk Vet. tid. 1977,29, 837–841.

    Google Scholar 

  • Kronevi T, Hansen Η J, Jonsson O J: Cerebellar hypoplasia of unknown etiology in pigs. Vet. Ree. 1975,96, 403–404.

    Article  CAS  Google Scholar 

  • Kronevi T, Lindquist J O: Mera om kongenital tremor (skaksjuke) hos gris. (More about congenital tremor in pigs. Case report). Svensk Vet. tid. 1978,50, 415–416.

    Google Scholar 

  • Marx J L: New information about the development of the autonomic nervous system. Science 1979,206, 434–437.

    Article  CAS  PubMed  Google Scholar 

  • Nafstad I, Berge G, Sannes E, Lyngset A: Teratogenic effects of the organophophorus compound fenchlorphos in rabbits. Acta vet. scand. 1983,24, 295–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robinson R J, Tigard JPM: Central nervous system in the new born. Brit. Med. Bull. 1966,22, 49–55.

    Article  CAS  PubMed  Google Scholar 

  • Rodier Ρ M: Chronology of neuron development: Animal studies and their clinical implications. Develop, med. Child Neurol. 1980,22, 525–545.

    Article  CAS  Google Scholar 

  • Saito Κ, Barber R, Wu J, Matsuda T, Roberts E, Vaughn J E: Immunohistochemical localization of glutamate decarboxylase in rat cerebellum. Proc. Natl. Acad. Sci. 1974,71, 269–273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sastry Β VR, Henderson G I: Kinetic mechanisms of human placental choline acetyltransferase. Bio-chem. Pharmacol. 1972,27, 787–802.

    Article  Google Scholar 

  • Sastry Β V R, Olubadewo J, Smidt D E: Placental cholinergic system and occurrence of acetylcholine in placenta. Fed. Proc. 1973, 32, 742.

    Google Scholar 

  • Schardein JL: Drugs as teratogens. CRC Press, Inc., Ohio, USA 1976, 77.

    Google Scholar 

  • Scheufler H: Der Einfluss relativ hoher Dosen von Dimethoat and Trichlorphon auf die Keimesent-wicklung der Labormaus. (Influence of relatively high dosis of dimethoat and trichlorfon on the embryonal development of the mouse). Biologis-che Rundschau 1975,13, 238–240.

    CAS  Google Scholar 

  • Schulman J A: Chemical neuroanatomy of the cerebellar cortex. In: Chemical Neuroanatomy, ed. P. C. Emson, Raven Press, New York 1983, p. 209–228.

    Google Scholar 

  • Staples R E, Goulding Ε H: Dipterex teratogenicity in the rat, hamster and mouse when given by gavage. Environm. Health Perspec. 1979, 30, 105–113.

    CAS  Google Scholar 

  • Sterri S H, Fonnum F: Isolation of organic anions by extraction with liquid anion exchangers and its application to micromethods for acetylcholinesterase and 4-aminobutyrate aminotransferase. Eur. J. Biochem. 1978,91, 215–222.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The authors wish to express their sincere thanks to professor Erling Sognen and professor Inger Nafstad for useful help, valuable advice and comments. The technical assistance of Mrs. E. Iversen, Mrs. Sidsel Sohlberg and Mr. T. Myrvold is greatly appreciated. This work was supported by grants from the Norwegian Agricultural Research Council.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology and Department of Internal Medicine, Norwegian College of Veterinary Medicine, P. O. Box 8146, Dep., N-0033, Oslo 1, Norway

    Gunnar N. Berge, Frode Fonnum & Per Brodai

  2. Norwegian Defence Research Establishment, Division for Toxicology, Kjeller, and University of Oslo, Anatomical Institute, Norway

    Gunnar N. Berge, Frode Fonnum & Per Brodai

Authors
  1. Gunnar N. Berge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frode Fonnum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Per Brodai
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Berge, G.N., Fonnum, F. & Brodai, P. Neurotoxic Effects of Prenatal Trichlorfon Administration in Pigs. Acta Vet Scand 28, 321–332 (1987). https://doi.org/10.1186/BF03548600

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1186/BF03548600

Keywords

  • teratogenicity
  • brain
  • transmitter enzymes

Acta Veterinaria Scandinavica

ISSN: 1751-0147