Journal of Neurocytology

, Volume 14, Issue 4, pp 563–578 | Cite as

A glutamate-sensitive neuronal system originating from the area postrema terminates in and transports acetylcholinesterase to the nucleus of the solitary tract

  • Sarolta Karcsú
  • Gábor Jancsó
  • Georg W. Kreutzberg
  • Lajos Tóth
  • Elizabeth Király
  • Ernö Bácsy
  • Ferenc A. László


The possible cellular mechanism of action of systemically administered monosodium-l-glutamate and the projections of glutamate-sensitive area postrema neurons have been studied in rats. Parenteral administration of monosodium-l-glutamate induced a selective degeneration of a particular population of AChE-containing area postrema neurons. Electron microscopic cytochemistry and X-ray microanalysis revealed the presence of calcium-containing electron-dense deposits in the mitochondria of degenerating area postrema neurons indicating the possible pathogenetic role of an enhanced intracellular calcium level in the mechanism of monosodium-l-glutamate-induced nerve cell degeneration. Degeneration of area postrema neurons was followed by the appearance of degenerating axon terminals in a well-defined region of the nucleus of the solitary tract, the area subpostrema. Degenerating area postrema neurons and axon terminals were rapidly engulfed by phagocytes predominantly of microglial character. AChE activity, localized to the basal lamina of the capillaries of the area subpostrema under normal conditions, could no longer be detected in rats treated with monosodium-l-glutamate 3–4 weeks previously.

These findings provide evidence for the existence of a particular population of glutamate-sensitive, AChE-containing area postrema neurons which project and transport AChE to the nucleus of the solitary tract. This specific neuronal pathway connecting the area postrema with the nucleus of the solitary tract may play an important role in some of the functions attributed to the area postrema. The results also strengthen the hypothesis that brain capillary AChE activity may be of neuronal origin.


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  1. Borison, H. L. (1974) Area postrema: chemoreceptor trigger zone for vomiting — is that all?Life Sciences 14, 1807–17.Google Scholar
  2. Burde, R. M., Schainker, B. &Kayes, J. (1971) Acute effect of oral and subcutaneous administration of monosodium glutamate on the arcuate nucleus of the hypothalamus in mice and rats.Nature 233, 58–60.Google Scholar
  3. Coil, J. D. &Norgren, R. (1981) Taste aversions conditioned with intravenous copper sulfate: attenuation by ablation of the area postrema.Brain Research 212, 425–33.Google Scholar
  4. Contreras, R. J. &Stetson, P. W. (1981) Changes in salt intake after lesions of the area postrema and the nucleus of the solitary tract in rats.Brain Research 211, 355–66.Google Scholar
  5. Csillik, B. &Sávay, Gy. (1963) Release of calcium in the myoneural junction.Nature 198, 399–400.Google Scholar
  6. Dalton, A. J. (1955) A chrome-osmium fixative for electron microscopy.Anatomical Record 121, 281 (Abstract).Google Scholar
  7. Edwards, G. L. &Ritter, R. C. (1981) Ablation of the area postrema causes exaggerated consumption of preferred foods in the rat.Brain Research 216, 265–76.Google Scholar
  8. Everly, J. L. (1971) Light microscopy examination of monosodium glutamate induced lesions in the brain of fetal and neonatal rats.Anatomical Record 169, 312 (Abstract).Google Scholar
  9. Farber, J. L. (1981) The role of calcium in cell death.Life Sciences 29, 1289–95.Google Scholar
  10. Fink, R. P. &Heimer, L. (1967) Two methods for selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system.Brain Research 4, 369–74.Google Scholar
  11. Fleckenstein, A., Janke, J., Doering, H. J. &Leder, O. (1974) Myocardial fiber necrosis due to intracellular Ca overload — a new principle in cardiac pathophysiology. InRecent Advances in Studies on Cardiac Structure and Metabolism Vol. 4 (edited byDhalla, N. S.), pp. 563–80. Baltimore: University Park Press.Google Scholar
  12. Flumerfelt, B. A., Lewis, P. R. &Gwyn, D. G. (1973) Cholinesterase activity of capillaries in the rat brain. A light and electron microscopic study.Histochemical Journal 5, 67–77.Google Scholar
  13. Greenfield, S. A., Chubb, I. W., Grünewald, R. A., Henderson, Z., May, J., Portnoy, S., Weston, J. &Wright, M. C. (1984) A non-cholinergic function for acetylcholinesterase in the substantia nigra: behavioural evidence.Experimental Brain Research 54, 513–20.Google Scholar
  14. Griffiths, T., Evans, M. C. &Meldrum, B. S. (1982) Intracellular sites of early calcium accumulation in the rat hippocampus during status epilepticus.Neuroscience Letters 30, 329–34.Google Scholar
  15. Holzwarth-Mcbride, M. A., Hurst, E. M. &Knigge, K. M. (1976) Monosodium glutamate induced lesions of the arcuate nucleus. I. Endocrine deficiency and ultrastructure of the median eminence.Anatomical Record 186, 185–96.Google Scholar
  16. Jancsó, G. (1978) Selective degeneration of chemosensitive primary sensory neurones induced by capsaicin: glial changes.Cell and Tissue Research 195, 145–52.Google Scholar
  17. Jancsó, G., Karcsú, S., Király, E., Szebeni, A., Tóth, L., Bácsy, E., Joó, F. &Párducz, Á. (1984) Neurotoxin induced nerve cell degeneration: possible involvement of calcium.Brain Research 295, 211–6.Google Scholar
  18. Jancsó, G. &Király, E. (1980) Distribution of chemosensitive primary sensory afferents in the central nervous system of the rat.Journal of Comparative Neurology 190, 781–92.Google Scholar
  19. Jancsó, G., Király, E. &Jancsó-Gábor, A. (1977) Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones.Nature 270, 741–3.Google Scholar
  20. Jancsó, G., Sávay, Gy. &Király, E. (1978) Appearance of histochemically detectable ionic calcium in degenerating primary sensory neurons.Acta histochemica 62, 165–9.Google Scholar
  21. Joó, F. &Csillik, B. (1966) Topographical correlation between the hematoencephalic barrier and the cholinesterase activity of brain capillaries.Experimental Brain Research 1, 147–51.Google Scholar
  22. Joy, M. D. &Loew, R. D. (1970) Evidence that the area postrema mediates the central cardiovascular response to angiotension II.Nature 228, 1303–4.Google Scholar
  23. Karcsú, S. &Tóth, L. (1975) Fine structural localization of acetylcholinesterase in capillaries surrounding the area postrema.Brain Research 95, 137–41.Google Scholar
  24. Karcsú, S. &Tóth, L. (1982) Die Veränderungen der Butyrylcholinesterase-Aktivität der fenestrierten Capillaren in der Area postrema während der postnatalen Entwicklung.Acta histochemica 71, 83–94.Google Scholar
  25. Karcsú, S., Jancsó, G. &Tóth, L. (1977) Butyrylcholinesterase activity in fenestrated capillaries of the rat area postrema.Brain Research 120, 146–50.Google Scholar
  26. Karcsú, S., Tóth, L., Jancsó, G. &Posberai, M. (1981a) Na-glutamat-sensitive Nervenzellen in der Area postrema bei der Ratte.Acta histochemica 68, 181–7.Google Scholar
  27. Karcsú, S., Tóth, L., Király, E. &Jancsó, G. (1981b) Evidence for the neuronal origin of brain capillary acetylcholinesterase activity.Brain Research 206, 203–7.Google Scholar
  28. Kása, P. &Csillik, B. (1966) Electron microscopic localization of cholinesterase by a copper-lead-thiocholine technique.Journal of Neurochemistry 13, 1345–9.Google Scholar
  29. Koelle, G. B. (1952) Histochemical localization of cholinesterases in the central nervous system of the rat.Journal of Pharmacology and Experimental Therapeutics 106, 401 (Abstract).Google Scholar
  30. Koelle, G. B. (1954) The histochemical localization of cholinesterases in the central nervous system of the rat.Journal of Comparative Neurology 100, 211–35.Google Scholar
  31. Kreutzberg, G. W. &Tóth, L. (1974) Dendritic secretion: a way for the neuron to communicate with the vasculature.Naturwissenschaften 61, 37–9.Google Scholar
  32. Kreutzberg, G. W. &Tóth, L. (1983) Enzyme cytochemistry of the cerebral microvessel wall.Acta neuropathologica Suppl. 8, 35–41.Google Scholar
  33. Kreutzberg, G. W., Kaiya, H. &Tóth, L. (1979) Distribution and origin of acetylcholinesterase activity in the capillaries of the brain.Histochemistry 61, 111–22.Google Scholar
  34. Kreutzberg, G. W., TÓth, L., Weikert, M. &Schubert, P. (1974) Changes in perineuronal capillaries accompanying chromatolysis of motoneurons. InPathology of Microcirculation (edited byCervos-Navarro, J. &Matakas, F.), pp. 282–8. Berlin, New York: Walter de Gruyter.Google Scholar
  35. Lemkey-Johnston, N. &Reynolds, W. A. (1974) Nature and extent of brain lesions in mice related to ingestion of monosodium glutamate. A light and electron microscope study.Journal of Neuropathology and Experimental Neurology 33, 74–97.Google Scholar
  36. Leonard, J. P. &Salpeter, M. M. (1979) Agonist-induced myopathy at the neuromuscular junction is mediated by calcium.Journal of Cell Biology 82, 811–9.Google Scholar
  37. Lewis, P. R. &Shute, C. C. D. (1966) The distribution of cholinesterase in cholinergic neurones demonstrated with the electron microscope.Journal of Cell Science 1, 381–90.Google Scholar
  38. Lichtensteiger, W. &Lienhart, R. (1977) Response of mesencephalic and hypothalamic dopamine neurones to α-MSH: mediated by area postrema?Nature 266, 635–7.Google Scholar
  39. Morest, D. K. (1960) A study of the structure of the area postrema with Golgi methods.American Journal of Anatomy 107, 291–303.Google Scholar
  40. Navaratnam, V. &Lewis, P. R. (1975) Effects of vagotomy on the distribution of cholinesterases in the cat medulla oblongata.Brain Research 100, 599–613.Google Scholar
  41. Olney, J. W. (1969) Brain lesions, obesity and other disturbances in mice treated with monosodium glutamate.Science 164, 719–21.Google Scholar
  42. Olney, J. W. (1971) Glutamate-induced neuronal necrosis in the infant mouse hypothalamus: an electron microscopic study.Journal of Neuropathology and Experimental Neurology 30, 75–90.Google Scholar
  43. Olney, J. W., Misra, C. H. &de Gubareff, T. (1975) Cysteine-S-sulfate: brain damaging metabolite in sulfite oxidase deficiency.Journal of Neuropathology and Experimental Neurology 34, 167–77.Google Scholar
  44. Olney, J. W., Rhee, V. &de Gubareff, T. (1977) Neurotoxic effects of glutamate on mouse area postrema.Brain Research 120, 151–7.Google Scholar
  45. Olney, J. W., Sharpe, L. G. &Feigin, R. D. (1972) Glutamate-induced brain damage in infant primates.Journal of Neuropathology and Experimental Neurology 31, 464–88.Google Scholar
  46. Oschman, J. L. &Wall, B. J. (1972) Calcium-binding to intestinal membranes.Journal of Cell Biology 55, 58–73.Google Scholar
  47. Price, M. T., Olney, J. W., Lowry, O. H. &Buchsbaum, S. (1981) Uptake of exogenous glutamate and aspartate by circumventricular organs but not other regions of brain.Journal of Neurochemistry 36, 1774–80.Google Scholar
  48. Reynolds, E. S. (1963) The use of lead citrate as an electron dense stain in electron microscopy.Journal of Cell Biology 17, 208–12.Google Scholar
  49. Salpeter, M. M., Kasprzak, H., Feng, H. &Fertugk, H. (1979) Endplates after esterase inactivationin vivo: correlation between esterase concentration, functional response and fine structure.Journal of Neurocytology 8, 95–115.Google Scholar
  50. Schanne, F. A. X., Kane, A. B., Young, E. E. &Farber, J. L. (1979) Calcium dependence of toxic cell death: a final common pathway.Science 206, 700–2.Google Scholar
  51. Somberg, J. C. &Smith, T. W. (1979) Localization of the neurally mediated arrhythmogenic properties of digitalis.Science 204, 321–3.Google Scholar
  52. Spačer, J. &Parižek, J. (1969) The fine structure of the area postrema of the rat.Acta morphologica Academiae scientiarum hungaricae 177, 17–34.Google Scholar
  53. Tafelski, T. J. (1976) Effects of monosodium glutamate on the neuroendocrine axis of the hamster.Anatomical Record 184, 543–4.Google Scholar
  54. Tóth, L. &Karcsú, S. (1976) Über die Lokalisation der Acetylcholinesterase in der Area postrema und Area subpostrema der Ratte. Licht- und elektronenhistochemische Untersuchungen.Acta histochemica 56, 245–60.Google Scholar
  55. Tóth, L., Karcsú, S., Poberai, M. &Sávay, Gy. (1981) A light and electron microscopic histochemical study on the mechanism of DFP-induced acute and subacute myopathy.Neuropathology and Applied Neurobiology 7, 399–410.Google Scholar
  56. Tóth, L., Karcsú, S., Poberai, M. &Sávay, Gy. (1983) Histochemical evidence for the role of Ca2+ and neutral protease in the development of the subacute myopathy induced by organophosphorous compounds.Acta histochemica 72, 71–5.Google Scholar

Copyright information

© Chapman and Hall Ltd 1985

Authors and Affiliations

  • Sarolta Karcsú
    • 1
  • Gábor Jancsó
    • 2
  • Georg W. Kreutzberg
    • 4
  • Lajos Tóth
    • 3
  • Elizabeth Király
    • 3
  • Ernö Bácsy
    • 5
  • Ferenc A. László
    • 1
  1. 1.Endocrine Unit, First Department of MedicineUniversity Medical SchoolSzegedHungary
  2. 2.Department of PhysiologyUniversity Medical SchoolSzegedHungary
  3. 3.Department of AnatomyUniversity Medical SchoolSzegedHungary
  4. 4.Max Planck Institute for PsychiatryMunichFRG
  5. 5.Institute of Experimental MedicineHungarian Academy of SciencesBudapestHungary

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