Neurochemical Research

, Volume 1, Issue 2, pp 141–152 | Cite as

Effects of selective doses of x-irradiation on the levels of several amino acids in the cerebellum of the rat

  • W. J. McBride
  • N. S. Nadi
  • J. Altman
  • M. H. Aprison
Article

Abstract

The cerebella of rats were exposed to selective doses of low levels of x-irradiation beginning on day 4, 8, or 12 following birth. The doses of x-irradiation given on days 12, 13, and 15 (12–15X group) resulted in a 24% reduction in the wet weight of the cerebella; the doses given on days 8, 9, 11, 13, and 15 (8–15X group) resulted in a 57% weight reduction; the doses given on days 4, 5, 7, 9, 11, 13, and 15 (4–15X group) resulted in a 67% weight reduction. The schedule of x-irradiation begun on day 12, which prevented the acquisition of the late-forming granule cells, reduced the levels (nmole/mg dry tissue weight) of alanine (22%) and glutamate (10%), and increased the levels of glycine (15%), GABA (13%), and taurine (71%), with respect to control values. The schedule begun on day 8, which prevented the acquisition of stellate and granule cells, reduced the levels of alanine (15%), glutamate (12%), and taurine (21%), and increased the levels of glycine (102%) and GABA (56%). The schedule begun on day 4, which prevented the acquisition of basket, stellate, and granule cells, reduced the level of glutamate (15%) and increased the levels of glycine (186%) and GABA (78%). The levels of alanine and taurine in the cerebella of the 4–15X group were the same as control values. The level of aspartate in the cerebella of the 3 groups of x-irradiated animals was not significantly different from control values. The consistent reduction in the level of glutamate as a function of the number of doses of x-irradiation is suggestive that glutamate may have a higher level in the granule cells than in other cells in the cerebellum, and that the higher level may be a reflection of a possible excitatory transmitter role for glutamate. In addition, the data are interpreted in terms of taurine being associated with the stellate cells and possibly serving as a transmitter for these inhibitory interneurons.

Keywords

Aspartate Glutamate Glycine Alanine Taurine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    McBride, W.J., Aprison, M.H., andKusano, K. (1976). Contents of several amino acids in the cerebellum, brain stem and cerebrum of the “staggerer,” “weaver” and “nervous” neurologically mutant mice. J. Neurochem. 26, 867–871.PubMedGoogle Scholar
  2. 2.
    Eccles, J.C., Ito, M., andSzentagothai, J. (1967). The cerebellum as a neuronal machine, Springer-Verlag, Berlin.Google Scholar
  3. 3.
    Altman, J. (1969). DNA metabolism and cell proliferation.In Lajtha, A. (ed.) Handbook of Neurochemistry, Volume II, Plenum Press, New York, pp. 137–182.Google Scholar
  4. 4.
    Altman, J. (1969). Autoradiographic and histological studies of postnatal neurogenesis. III. Dating the time of production and onset of differentiation of cerebellar microneurons in rats. J. Comp. Neur. 136, 269–294.PubMedGoogle Scholar
  5. 5.
    Hicks, S.P. andD'Amato, C.J. (1966). Effects of ionizing radiations on mammalian development.In Woollam, D.H.M. (ed.), Advances in Teratology, Logos Press, London, pp. 195–250.Google Scholar
  6. 6.
    Altman, J., andAnderson, W.J. (1971). Irradiation of the cerebellum in infant rats with low level x-ray: histological and cytological effects during infancy and adulthood. Exp. Neurol. 39, 492–509.Google Scholar
  7. 7.
    Altman, J., Anderson, W.J., andWright, K.A. (1967). Selective destruction of precursors of microneurons of the cerebellar cortex with fractionated low-dose x-rays. Exp. Neurol. 17, 481–497.PubMedGoogle Scholar
  8. 8.
    Altman, J., Anderson, W.J., andWright, K.A. (1968). Gross morphological consequences of irradiation of the cerebellum in infant rats with repeated doses of lowlevel x-ray. Exp. Neurol. 21, 69–91.Google Scholar
  9. 9.
    Altman, J., andAnderson, W.J. (1972). Experimental reorganization of the cerebellar cortex. I. Morphological effects of elimination of all microneurons with prolonged x-irradiation started at birth. J. Comp. Neurol. 146, 355–369.PubMedGoogle Scholar
  10. 10.
    Aprison, M.H., andWerman, R. (1968). A combined neurochemical and neurophysiological approach to the identification of central nervous system transmitters.Ehrenpreis, S., andSolnitzky, O.C. (eds.), Neurosciences Research, Volume 1, Academic Press, New York, pp. 143–156.Google Scholar
  11. 11.
    Kawamura, H., andProvini, L. (1970). Depression of cerebellar Purkinje cells by microiontophoretic application of GABA and related amino acids. Brain Res. 24, 293–304.PubMedGoogle Scholar
  12. 12.
    Obata, K. (1969). Gamma-aminobutyric acid in Purkinje cells and motoneurones. Experientia 25, 1283.PubMedGoogle Scholar
  13. 13.
    Obata, K., Ito, M., Ochi, R., andSato, N. (1967). Pharmacological properties of the postsynaptic inhibition by Purkinje cell axons and the action of γ-aminobutyric acid on Deiter's neurones. Exp. Brain Res. 4, 43–57.PubMedGoogle Scholar
  14. 14.
    Shank, R.P., andAprison, M.H. (1970). The metabolismin vivo of glycine and serine in eight areas of the rat central nervous system. J. Neurochem. 17, 1461–1475.PubMedGoogle Scholar
  15. 15.
    Curtis, D.R., andWatkins, J.C. (1960). The excitation and depression of spinal neurones by structurally related amino acids. J. Neurochem. 6, 117–141.PubMedGoogle Scholar
  16. 16.
    Altman, J. (1975). Experimental reorganization of the cerebellar aortex. VII. Effects of late x-irradiation schedules that interfere with cell acquisition after stellate cells are formed. J. Comp. Neurol. 165, 65–76.Google Scholar
  17. 17.
    Altman, J. (1975). Experimental reorganization of the cerebellar cortex. VI. Effect of x-irradiation schedules that allow or prevent cell acquisition after basket cells are formed. J. Comp. Neurol. 165, 49–64.Google Scholar
  18. 18.
    Altman, J., andAnderson, W.J. (1973). Experimental reorganization of the cerebellar cortex. II. Effects of elimination of most microneurons with prolonged x-irradiation started at four days. J. Comp. Neurol. 149, 123–152.PubMedGoogle Scholar
  19. 19.
    Altman, J. (1975). Experimental reorganization of the cerebellar cortex. V. Effects of early x-irradiation schedules that allow or prevent the acquisition of basket cells. J. Comp. Neurol. 165, 31–48.Google Scholar
  20. 20.
    Aprison, M.H., McBride, W.J., andFreeman, A.R. (1973). The distribution of several amino acids in specific ganglia and nerve bundles of the lobster. J. Neurochem. 21, 87–95.PubMedGoogle Scholar
  21. 21.
    Smith, J.E., Lane, J.D., Shea, P.A., McBride, W.J., andAprison, M.H. (1975). A method for concurrent measurement of picomole quantities of acetylcholine, choline, dopamine, norepinephrine, serotonin, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, tryptophan, tyrosine, glycine, aspartate, glutamate, alanine, and gammaaminobutyric a acid in single tissue samples from different areas of rat central nervous system. Anal. Biochem. 64, 149–169.PubMedGoogle Scholar
  22. 22.
    Beart, P.M., andSnodgrass, S.R. (1975). The use of a sensitive double isotope dansylation technique for amino acid analysis. J. Neurochem. 24, 821–825.PubMedGoogle Scholar
  23. 23.
    Young, A.B., Oster-Granite, M.L., Herndon, R.M., andSnyder, S.H. (1974). Glutamic acid: selective depletion by viral induced granule cell loss in hamster cerebellum. Brain Res. 73, 1–14.PubMedGoogle Scholar
  24. 24.
    Graham, L.T., Jr., Shank, R.P., Werman, R., andAprison, M.H. (1967). Distribution of some synaptic transmitter suspects in cat spinal cord: glutamic acid, aspartic acid, γ-aminobutyric acid, glycine and glutamine. J. Neurochem. 14, 465–472.PubMedGoogle Scholar
  25. 25.
    Johnson, J. (1972). Glutamic acid as a synaptic transmitter in the nervous system. A review. Brain Res. 37, 1–19.PubMedGoogle Scholar
  26. 26.
    Johnson, J., andAprison, M.H. (1970). The distribution of glutamic acid, a transmitter candidate, and other amino acids in the dorsal sensory neuron of the cat. Brain Res. 24, 285–292.PubMedGoogle Scholar
  27. 27.
    Shank, R.P., Freeman, A.R., McBride, W.J., andAprison, M.H. (1975). Glutamate and aspartate as mediators of neuromuscular excitation in the lobster. Comp. Biochem. Physiol. 50C, 127–131.Google Scholar
  28. 28.
    Geller, H.M., andWoodward, D.J. (1974). Responses of cultured cerebellar neurons to iontophoretically applied amino acids. Brain Res. 74, 67–80.PubMedGoogle Scholar
  29. 29.
    Woodward, D.J., Hoffer, B.J., andAltman, J. (1974). Physiological and pharmacological properties of Purkinje cells in rat cerebellum degranulated by postnatal x-irradiation. J. Neurobiol. 5, 283–304.PubMedGoogle Scholar
  30. 30.
    Woodward, D.J., Hoffer, B.J., Siggins, G.R., andBloom, F.E. (1971). The ontogenetic development of synaptic junctions. Synaptic activation and responsiveness to neurotransmitter substances in rat cerebellar Purkinje cells. Brain Res. 34, 73–98.PubMedGoogle Scholar
  31. 31.
    Chujo, J., Yamada, Y., andYamamoto, C. (1975). Sensitivity of Purkinje cell dendrites to glutamic acid. Exp. Brain Res. 23. 293–300.PubMedGoogle Scholar
  32. 32.
    Ferrendelli, J.A., Chang, M.M., andKinscherf, D.A. (1974). Elevation of cyclic GMP levels in central nervous system by excitatory and inhibitory amino acids. J. Neurochem. 22, 535–540.PubMedGoogle Scholar
  33. 33.
    Ferrendelli, J.A., Kinscherf, D.A., andChang, M.M. (1973). Regulation of levels of guanosine 3′, 5′-monophosphate in the central nervous system. Effects of depolarizing agents. Mol. Pharmacol. 9, 445–454.PubMedGoogle Scholar
  34. 34.
    Kuo, J.F., Lee, T.P., Reyes, P.L., Walton, K.G., Donnelly, T.E., andGreengard, P. (1972). Cyclic nucleotide dependent protein kinases: an assay method for the measurement of guanosine 3′, 5′-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J. Biol. Chem. 247, 16–22.PubMedGoogle Scholar
  35. 35.
    Mao, C.C., Guidotti, A., andCosta, E. (1974). The regulation of cyclic guanosine monophosphate in rat cerebellum: possible involvement of putative amino acid neurotransmitters. Brain Res. 79, 510–514.PubMedGoogle Scholar
  36. 36.
    Mao, C.C., Guidotti, A., andLandis, S. (1975). Cyclic GMP: reduction of cerebellar concentrations in nervous mutant mice. Brain Res. 90, 335–339.PubMedGoogle Scholar
  37. 37.
    Kuriyama, K., Habor, B., Sisken, B., andRoberts, E. (1966). The γ-aminobutyric acid system in rabbit cerebellum. Proc. Natl. Acad. Sci. U.S. 55, 846–852.Google Scholar
  38. 38.
    Bisti, S., Iosif, G., andStrata, P. (1971). Suppression of inhibition in the cerebellar cortex by picrotoxin and bicuculline. Brain Res. 28, 591–593.PubMedGoogle Scholar
  39. 39.
    Curtis, D.R., Duggan, A.W., Felix, D., andJohnston, G.A.R. (1970). GABA, bicuculline and central inhibition. Nature 226, 1222–1224.PubMedGoogle Scholar
  40. 40.
    McLaughlin, B.J., Wood, J.G., Saito, K., Barber, R., Vaughn, J.E., Roberts, E., andWu, J.-Y. (1974). The fine structural localization of glutamate decarboxylase in synaptic terminals of rodent cerebellum. Brain Res. 76, 377–392.PubMedGoogle Scholar
  41. 41.
    Schon, F., andIversen, L.L. (1972). Selective accumulation of [3H] GABA by stellate cells in rat cerebellar cortexin vivo. Brain Res. 42, 503–507.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1976

Authors and Affiliations

  • W. J. McBride
    • 1
  • N. S. Nadi
    • 1
  • J. Altman
    • 2
    • 1
  • M. H. Aprison
    • 1
  1. 1.Section of Basic Neural Sciences, Institute of Psychiatric Research and Departments of Psychiatry and BiochemistryIndiana University School of MedicineIndianapolis
  2. 2.Laboratory of Developmental Neurobiology Department of Biological SciencesPurdue UniversityLafayette

Personalised recommendations