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Excitatory Amino Acid Receptor Antagonist in Murine Motoneuron Disease (The Wobbler Mouse)

Published online by Cambridge University Press:  18 September 2015

Charles Krieger ,
Thomas L. Perry ,
Shirley Hansen ,
Hiroshi Mitsumoto  and
Tage Honoré
Charles Krieger*
Affiliation:
Division of Neurology, Department of Medicine, Vancouver
Thomas L. Perry
Affiliation:
Department of Medicine, Department of Pharmacology and Therapeutics, Vancouver
Shirley Hansen
Affiliation:
Department of Medicine, Department of Pharmacology and Therapeutics, Vancouver
Hiroshi Mitsumoto
Affiliation:
The University of British Columbia, Vancouver; Department of Neurology, The Cleveland Clinic Foundation, Cleveland
Tage Honoré
Affiliation:
Novo Nordisk A/S, CNS Division, Sydmarken 5, Soeborg, Denmark
*
Division of Neurology, Department of Medicine, 2211 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1W5
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Abstract:

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Recent evidence has suggested a potential role for involvement of excitatory amino acids (EAA) in the pathogenesis of the neuron loss in motoneuron diseases. We have examined the ability of an antagonist of N-methyl-D-aspartate (NMDA) receptors to halt or retard the progression of neurological symptoms in a murine form of motoneuron disease. The wobbler mouse is an autosomal recessive mutant which develops progressive neurological symptoms secondary to motoneuron loss. Treatment of wobbler mice with the NMDA receptor antagonist (+)-5-methyl-10,l 1-dihydro-5H-dibenzo(a,d)cyclohepten-5, 10-imine maleate (MK-801) did not retard neurological deterioration as assessed by a semiquantitive clinical scale. We conclude that NMDA receptor activation is probably not involved in the pathogenesis of motoneuron loss in the wobbler mouse.

Type
Articles
Information
Canadian Journal of Neurological Sciences , Volume 19 , Issue 4 , November 1992 , pp. 462 - 465
Copyright
Copyright © Canadian Neurological Sciences Federation 1992

References

REFERENCES

1.Plaitakis, A, Caroscio, JT.Abnormal glutamate metabolism in amyotrophic lateral sclerosis. Ann Neurol 1987; 22: 575–579.CrossRefGoogle ScholarPubMed
2.Plaitakis, A, Constantakakis, E, Smith, J.The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosis. Ann Neurol 1988; 24: 446–449.CrossRefGoogle ScholarPubMed
3.Rothstein, JD.Tsai, G, Kuncl, RW, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 1990; 28: 18–25.CrossRefGoogle ScholarPubMed
4.Spencer, PS, Nunn, PB, Hugon, J, et al. Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science 1987; 237: 517–522.CrossRefGoogle ScholarPubMed
5.Biscoe, TJ, Evans, RH, Headley, PM, et al. Structure-activity relations of excitatory amino acids on frog and vat spinal neurons. Br J Pharmacol 1976; 58: 373–382.CrossRefGoogle Scholar
6.O’Brien, RJ, Fischbach, GD.Characterization of excitatory amino acid receptors expressed by embryonic chick motoneurons in vitro. J Neurosci 1986; 6: 3275–3283.CrossRefGoogle ScholarPubMed
7.Teitelbaum, JS, Zatorre, RJ, Carpenter, S, et al. Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. N Engl J Med 1990; 322: 1781–1787.CrossRefGoogle Scholar
8.Perry, TL, Krieger, C, Hansen, S, et al. Amyotrophic lateral sclerosis: amino acid levels in plasma and cerebrospinal fluid. Ann Neurol 1990; 28: 12–17.CrossRefGoogle ScholarPubMed
9.Perry, TL, Hansen, S, Jones, K.Brain glutamate deficiency in amyotrophic lateral sclerosis. Neurology 1987; 37: 1845–1848.CrossRefGoogle ScholarPubMed
10.Tsai, G, Stauch-Slusher B. Sim, L, et al. Reductions in acidic amino acids and N-acetylaspartylglutamate in amyotrophic lateral sclerosis CNS. Brain Res 1991; 556: 151–156.CrossRefGoogle ScholarPubMed
11.Allaoua, H, Chaudieu, I, Krieger, C, et al. Alterations in spinal cord excitatory amino acids receptors in amyotrophic lateral sclerosis patients. Brain Res 1992; 579: 169–172.CrossRefGoogle ScholarPubMed
12.Duchen, LW.Motor neuron diseases in man and animals. Invest Cell Pathol 1978; 1: 249–262.Google ScholarPubMed
13.Duchen, LW.Strich, SJ, Falconer, DS.An hereditary motor neurone disease with progressive denervation of muscle in the mouse: the mutant “wobbler”. J Neurol Neurosurg Psychiatry 1968; 31: 535–542.CrossRefGoogle ScholarPubMed
14.Krieger, C, Perry, TL, Hansen, S.et al. The wobbler mouse: amino acid contents in brain and spinal cord. Brain Res 1991; 551: 142–144.CrossRefGoogle ScholarPubMed
15.Wong, EHF, Kemp, JA, Priestley, T, et al. The anticonvulsant MK-801 is a potent N-methyl-D-asparate antagonist. Proc Natl Acad Sci USA 1986; 83: 7104–7108.CrossRefGoogle Scholar
16.Perry, TL, Bergeron, C, Biro, AJ, et al. B-N-Methylamino-L-alanine: chronic oral administration is not neurotoxic to mice. J Neurol Sci 1989; 94: 173–180.CrossRefGoogle Scholar
17.Krieger, C, Perry, TL, Hansen, S, et al. Excitatory amino acid receptor antagonists in murine motoneuron disease. Can J Neurol Sci 1991; 18: 261.Google Scholar
18.Kozachuk, WE, Mitsumoto, H, Salanga, VD, et al. Thyrotropin-releasing hormone (TRH) in murine motor neuron disease (the wobbler mouse). J Neurol Sci 1987; 78: 253–260.CrossRefGoogle ScholarPubMed
19.Holland, BS, Copenhaver, MD.Improved Bonferroni-type multiple testing procedures. Psych Bull 1988; 104: 145–149.CrossRefGoogle Scholar