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Trophic factor effects on cholinergic innervation in the cerebral cortex of the adult rat brain

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Abstract

The cholinergic pathway ascending from the nucleus basalis magnocellularis (NBM) to the cortex has been implicated in several important higher brain functions such as learning and memory. Following infarction of the frontoparietal cortical area in the rat, a retrograde atrophy of cholinergic cell bodies and fiber networks occurs in the basalocortical cholinergic system. We have observed that neuronal atrophy in the NBM induced by this lesion can be prevented by intracerebroventricular administration of exogenous nerve growth factor (NGF) or the monosialoganglioside GM1. In addition, these agents can upregulate levels of cortical choline acetyltransferase (ChAT) activity in the remaining cortex adjacent to the lesion site. Furthermore, an enhancement in cortical high-affinity3H-choline uptake and a sustained in vivo release of cortical acetylcholine (ACh) after K+ stimulation are also observed after the application of neurotrophic agents. Moreover, these biochemical changes in the cortex are accompanied by an anatomical remodeling of cortical ChAT-immunoreactive fibers and their synaptic boutons.

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References

  • Batchelor P. E., Armstrong D. M., Blaker S. N., and Gage F. H. (1989) Nerve growth factor receptor and choline acetyltransferase colocalization in neurons within the rat forebrain: response to fimbria-fornix transection.J. Comp. Neurol. 284, 187–204.

    Article  PubMed  CAS  Google Scholar 

  • Benveniste H. (1989) Brain microdialysis.J. Neurochem. 52, 1667–1679.

    Article  PubMed  CAS  Google Scholar 

  • Brodsky F. M. (1988) Living with clathrin: its role in intracellular membrane traffic.Science 242, 1396–1402.

    Article  PubMed  CAS  Google Scholar 

  • Casamenti F., Deffenu G., Abbamondi A. L., and Pepeu G. (1986) Changes in cortical acetylcholine output induced by modulation of the nucleus basalis.Brain Res. Bull. 16, 689–695.

    Article  PubMed  CAS  Google Scholar 

  • Chandler C. E., Parsons LM., Hosang M., and Shooter E. M. (1984) A monoclonal antibody modulates the interaction of nerve growth factor with PC12 cells.J. Biol. Chem. 259, 6882–6889.

    PubMed  CAS  Google Scholar 

  • Cuello A. C. (1990) Glycosphingolipids that can regulate nerve growth and repair,Advances in Pharmacology, Academic, New York, pp. 1–50.

    Google Scholar 

  • Cuello A. C., Garofalo L., Kenigsberg R. L., and Maysinger D. (1989) Gangliosides potentiatein vivo andin vitro effects of nerve growth factor on central cholinergic neurons.Proc. Natl. Acad. Sci. USA 86, 2056–2060.

    Article  PubMed  CAS  Google Scholar 

  • Cuello A. C., Pioro E. P., and Ribeiro-da-Silva A. (1990) Cellular and subcellular localization of nerve growth factor receptor-like immunoreactivity in the rat CNS.Neurochem. Int. 17, 205–213.

    Article  CAS  Google Scholar 

  • Dawbarn D., Allen S. J., and Semenenko F. M. (1988) Coexistence of choline acetyltransferase and nerve growth factor receptors in the rat basal forebrain.Neurosci. Lett. 94, 138–144.

    Article  PubMed  CAS  Google Scholar 

  • DeRobertis E. P. (1964)Histophysiology of Synapses and Neurosecretion, Pergamon, Oxford, UK.

    Google Scholar 

  • DiPatre P. L., Casamenti F., Cenni A., and Pepeu G. (1989) Interaction between nerve growth factor and GM1 monosialoganglioside in preventing cortical choline acetyltransferase and high-affinity choline uptake decrease after lesion of the nucleus basalis.Brain Res. 480, 219–224.

    Article  CAS  Google Scholar 

  • Eckenstein F. (1988) Transient expression of NGF-receptor-like immunoreactivity in postnatal rat brain and spinal cord.Brain Res. 446, 149–154.

    Article  PubMed  CAS  Google Scholar 

  • Elliott P. J., Garofalo L., and Cuello A. C. (1989) Limited neocortical devascularizing lesions causing deficits in memory retention and choline acetyltransferase activity: effects of the monosialoganglioside GM1.Neuroscience 31, 63–76.

    Article  PubMed  CAS  Google Scholar 

  • Garofalo L. and Cuello A. C. (1989) Effects of NGF and/or GM1 on high-affinity choline uptake in the rat brain following unilateral decortication.Soc. Neurosci. Abstr. 15, 867.

    Google Scholar 

  • Garofalo L. and Cuello A. C. (1990) Nerve growth factor and the monosialoganglioside GM1 modulate cholinergic markers and affect behavior of decorticated adult rats.Euro. J. Pharmacol. 183, 934.

    Article  Google Scholar 

  • Goldstein J. L., Anderson R. G. W., and Brown M. S. (1979) Coated pits, coated vesicles and receptor-mediated endocytosis.Nature 279, 679–685.

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Pinilla F., Cotman C. W., and Nieto-Sampedro M. (1987) NGF-receptor immunoreactivity in rat brain: topographical distribution and response to entorhinal ablation.Neurosci. Lett. 82, 260–266.

    Article  PubMed  CAS  Google Scholar 

  • Hefti F., Hartikka J., and Knusel B. (1989) Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurode-generative diseases.Neurobiol. Aging 10(5), 515–533.

    Article  PubMed  CAS  Google Scholar 

  • Hefti F., Hartikka J., Salvatierra A., Weiner W. J., and Mash D. C. (1986) Localization of nerve growth factor receptors in cholinergic neurons of the human basal forebrain.Neurosci. Lett. 69, 37–41.

    Article  PubMed  CAS  Google Scholar 

  • Hempstead B. L., Martin-Zanca D., Kaplan D. R., Parada L. F., and Chao M. V. (1991) High-affinity NGF-binding requires coexpression of thetrk protooncogene and the low-affinity NGF receptor.Nature 350, 678–683.

    Article  PubMed  CAS  Google Scholar 

  • Hyman C., Hofer M., Barde Y. A., Juhasz M., Yancopoulos G. D., Squinto S. P., and Lindsay R. M. (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra.Nature 350, 230–232.

    Article  PubMed  CAS  Google Scholar 

  • Johnston M. V., McKinney M., and Coyle J. T. (1981) Neocortical cholinergic innervation: a description of extrinsic and intrinsic components in the rat.Expl. Brain Res. 43, 159–172.

    CAS  Google Scholar 

  • Kaplan D. R., Hempstead B. L., Martin-Zanca D., Chao M. V., and Parada L. F. (1991) Thetrk proto-oncogene product: a signal transducing receptor for nerve growth factor.Science 252, 554–558.

    Article  PubMed  CAS  Google Scholar 

  • Kiss J., McGovern J., and Patel A. J. (1988) Immuno-histochemical localization of cells containing nerve growth factor receptors in the different regions of the adult rat forebrain.Neuroscience 27, 731–748.

    Article  PubMed  CAS  Google Scholar 

  • Koh S. and Loy R. (1989) Localization and development of nerve growth factor-sensitive rat asal forebrain neurons and their afferent projections to hippocampus and neocortex.J. Neurosci. 9, 2999–3018.

    PubMed  CAS  Google Scholar 

  • Kromer L. F. (1987) Nerve growth factor treatment after brain injury prevents neuronal death.Science 235, 214–216.

    Article  PubMed  CAS  Google Scholar 

  • Levi-Montalcini R. and Angeletti P. U. (1968) Nerve growth factor.Physiol. Rev. 48, 534–569.

    PubMed  CAS  Google Scholar 

  • Maisonpierre P. C., Belluscio L., Squinto S., Ip N. Y., Furth M. E., Lindsay R. M., and Yancopoulos G. D. (1990) Neurotrophin-3: a neurotrophic factor related to NGF and BDNF.Science 247, 1446–1451.

    Article  PubMed  CAS  Google Scholar 

  • Maysinger D. Herrera-Marschitz M., Carlsson A., Garofalo L., Ungerstedt U., and Cuello A. C. (1988) Striatal and cortical acetylcholine releasein vivo in rats with unilateral decortication: effects of treatment with monosialoganglioside GM1.Brain Res. 461, 355–360.

    Article  PubMed  CAS  Google Scholar 

  • Maysinger D., Herrera-Marschitz M., Ungerstedt U., and Cuello A. C. (1990a) Acetylcholine releasein vivo: effects of chronic treatment with monosi-aloganglioside GM1.Neuropharmacology 29(2), 151–159.

    Article  PubMed  CAS  Google Scholar 

  • Maysinger D., Herrera-Marschitz M., Ungerstedt U., and Cuello A. C. (1990b) Relaase of acetylcholine from cerebral cortexin vivo: effects of NGF and GM1.Euro. J. Pharmacol. 83(3), 935.

    Article  Google Scholar 

  • Oppenheim R. W., Prevette D., Qin-Qei Y., Collins F., and MacDonald J. (1991) Control of embryonic motoneuron survivalin vivo by ciliary neurotrophic factor.Science 251, 1616–1618.

    Article  PubMed  CAS  Google Scholar 

  • Pepeu G (1983) Brain acetylcholine: an inventory of our knowledge on the 50th anniversary of its discovery.Trends Pharmacol. Sci. 4, 416–418.

    Article  CAS  Google Scholar 

  • Pioro, E. P. and Cuello A. C. (1990) Distribution of nerve growth factor receptor-like immunore-activity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system: forebrain.Neuroscience 34, 57–87.

    Article  PubMed  CAS  Google Scholar 

  • Pioro E. P., Ribeiro-da-Silva A., and Cuello A. C. (1988) Electron microscopy of nerve growth factor receptor immunoreactivity in cerebellar Purkinje cells of adult rats pretreated with colchicine.Abstr. Soc. Neurosci. 14, 903.

    Google Scholar 

  • Pioro E. P., Ribeiro-da-Silva A., and Cuello A. C. (1990) Immunoelectron microscopic evidence of nerve growth factor receptor metabolism and internalization in rat nucleus basalis neuronsBrain Res. 527, 109–115.

    Article  PubMed  CAS  Google Scholar 

  • Schweitzer J. B. (1987) Nerve growth factor receptor-mediated transport from cerebrospinal fluid to basal forebrain neurons.Brain Res. 423, 309–317.

    Article  PubMed  CAS  Google Scholar 

  • Seiler M. and Schwab M. E. (1984) Specific retrograde transport of nerve growth factor from neocortex to nucleus basalis in the rat.Brain Res. 300, 33–39.

    Article  PubMed  CAS  Google Scholar 

  • Simon J. R., Atweh S., and Kuhar M. J. (1976) Sodium dependent high-affinity choline uptake: a regulatory step in the synthesis of acetylcholine.J. Neurochem. 26, 909–922.

    Article  PubMed  CAS  Google Scholar 

  • Skaper S. D., Katoh-Semba R., and Varon S. (1985) GM1 ganglioside accelerates neurite outgrowth from primary peripheral and central neurons under selective culture conditions.Dev. Brain Res. 23, 19–26.

    Article  CAS  Google Scholar 

  • Sofroniew M. V., Isaacson O., and O'Brien T. S. (1988) Nerve growth factor receptor immunoreactivity in the rat suprachiasmatic nucleus.Brain Res. 476, 358–362.

    Article  Google Scholar 

  • Sofroniew M. V., Pearson R. C. A., Eckenstein F., Cuello A. C., and Powell T. P. S. (1983) Retrograde changes in cholinergic neurons in the basal forebrain of the rat following cortical damage.Brain Res. 289, 370–374.

    Article  PubMed  CAS  Google Scholar 

  • Springer J. E., Koh S., Tayrien M. W., and Loy R. (1987) Basal forebrain magnocellular neurons stain for nerve growth factor receptor: correlation with cholinergic cell bodies and effects of axotomy.J. Neurosci. Res. 17, 111–118.

    Article  PubMed  CAS  Google Scholar 

  • Stephens, P. H., Cuello A. C., Sofroniew M. V., Pearson R. C. A., and Tagari P. (1985) Effect of unilateral decortication on choline acetyltransferase activity in the nucleus basalis and other areas of the rat brain.J. Neurochem. 45, 1021–1026.

    Article  PubMed  CAS  Google Scholar 

  • Taniuchi M. and Johnson, E. M. Jr. (1985) Characterization of the binding properties and retrograde axonal transport of a monoclonal antibody directed against the rat nerve growth factor receptor.J. Cell Biol. 101, 1100–1106.

    Article  PubMed  CAS  Google Scholar 

  • Taniuchi M., Schweitzer J. B., and Johnson, E. M. Jr. (1986) Nerve growth factor receptor molecules in rat brain.Proc. Natl. Acad. Sci. USA 83, 1950–1954.

    Article  PubMed  CAS  Google Scholar 

  • Ungerstedt U. (1984) Measurement of neurotransmitter release by intracranial dialysis,Measurement of Neurotransmitter Release In Vivo, Wiley, New York, pp. 81–107.

    Google Scholar 

  • Vantini G., Fusco M., Bigon E., and Leon A. (1988) GM1 ganglioside potentiates the effect of nerve growth factor in preventing vinblastine induced sympathectomy in newborn rats.Brain Res. 448, 252–258.

    Article  PubMed  CAS  Google Scholar 

  • Williams L. R., Varon S., Peterson G. M., Wictorin K., Fischer W., Björklund A., and Gage F. H. (1986) Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection.Proc. Natl. Acad. Sci. USA 83, 92131–9235.

    Google Scholar 

  • Yan Q. and Johnson E. M. Jr. (1988) An immunohistochemical study of the nerve growth factor receptor in developing rats.J. Neurosci. 8, 3481–3498.

    PubMed  CAS  Google Scholar 

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Cuello, A.C., Maysinger, D. & Garofalo, L. Trophic factor effects on cholinergic innervation in the cerebral cortex of the adult rat brain. Mol Neurobiol 6, 451–461 (1992). https://doi.org/10.1007/BF02757946

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