Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 334, Issue 4, pp 346–351 | Cite as

Cholinergic but not monoaminergic denervation increases nerve growth factor content in the adult rat hippocampus and cerebral cortex

  • G. Weskamp
  • H. P. Lorez
  • H. H. Keller
  • U. Otten
Article

Summary

We have investigated whether degeneration of basal forebrain cholinergic neurons is a potential trigger for increased NGF production in the adult rat brain. Electrolytic lesions of cholinergic neurons in the septum-diagonal band and in the nucleus basalis of Meynert induced a transient increase in NGF in the ventral hippocampus (+70%) and cerebral cortex (+125%), respectively. In contrast, selective aminergic denervation of the forebrain by electrolytic lesion of the medial forebrain bundle, did not increase NGF levels in hippocampus and cerebral cortex. Thus, a cholinergic mechanism appears to regulate NGF production in adult rat basal forebrain.

Key words

Nerve growth factor (NGF) Rat basal forebrain Cholinergic neurons Monoaminergic neurons Denervation 

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References

  1. Bigl V, Woolf NJ, Butcher LL (1982) Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital and cingulate cortices: a combined fluorescent tracer and acetyl-cholinesterase analysis. Brain Res Bull 8:727–749Google Scholar
  2. Björklund A, Stenevi U (1981) In vivo evidence for a hippocampal adrenergic neuronotrophic factor specifically released on septal deafferentiation. Brain Res 229:403–428Google Scholar
  3. Collins F, Crutcher KA (1985) Neuronotropnic activity in the adult rat hippocampal formation: regional distribution and increase after septal lesion. J Neurosci 5:2809–2814Google Scholar
  4. Cotman CW, Nieto-Sampedro M (1984) Cell biology of synaptic plasticity. Science 225:1287–1293Google Scholar
  5. Cuello CA, Sofroniew MV (1984) The anatomy of the CNS cholinergie neurons. TINS 7:74–78Google Scholar
  6. Crutcher KA, Brothers L, Davis JN (1981) Sympathetic noradrenergic sprouting in response to central cholinergic denervation: A histochemical study of neuronal sprouting in the rat hippocampal formation. Brain Res 210:115–128Google Scholar
  7. Ebendal T, Olson L, Sciger A, Hedlund K-O (1980) Nerve growth factor in the rat iris. Nature 286:25–28Google Scholar
  8. Fibiger HG (1982) The organization and some projections of cholinergic neurons of the mammalian forebrain. Brain Res Rev 4:327–388Google Scholar
  9. Fonnum F (1975) A rapid radiochemical method for the determination of choline acetyltransferase. J Neurochem 24:407–409Google Scholar
  10. Fonnum F, Walaas J (1978) The effect of intrahippocampal kainic acid injections and surgical lesions on neurotransmitters in hippocampus and septum. J Neurochem 31:1173–1181Google Scholar
  11. Gage FH, Björklund A, Stenevi U (1983) Reinnervation of the partially deafferented hippocampus by compensatory collateral sprouting from spared cholinergic and noradrenergic afferents. Brain Res 268:27–37Google Scholar
  12. Gage FH, Björklund A, Stenevi U (1984) Denervation releases a neuronal survival factor in adult rat hippocampus. Nature 308:637–639Google Scholar
  13. Gasser UE, Weskamp G, Otten U, Dravid AR (1986) Lesions of the septo-hippocampal pathway in rats induce elevation of nerve growth factor (NGF) content in the hippocampus and septum. Brain Res 376:351–356Google Scholar
  14. Gnahn H, Hefti F, Heumann R, Schwab ME, Thoenen H (1983) NGF-mediated increase of choline acetyltransferase (ChAT) in the neonatal rat forebrain: evidence for a physiological role of NGF in brain? Develop Brain Res 9:45–52Google Scholar
  15. Hefti F, Dravid A, Hartikka J (1984) Chronic intraventricular injection of nerve growth factor elevates hippocampal choline acetyltransferase-activity in adult rats with partial septohippocampal lesions. Brain Res 293:305–311Google Scholar
  16. Henderson CE, Huchet M, Changeux JP (1983) Denervation increases a neurite-promoting activity in extracts of skeletal muscle. Nature 302:609–611Google Scholar
  17. König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. The Williams and Wilkins Co, Baltimore, MdGoogle Scholar
  18. Korsching S, Auburger G, Heumann R, Scott J, Thoenen H (1985) Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlates with the cholinergic innervation. EMBO J 4:1389–1393Google Scholar
  19. Large TH, Bodary SC, Clegg DO, Weskamp G, Otten U, Reichardt LF (1986) Nerve growth factor gene expression in the developing rat brain. Science (in press)Google Scholar
  20. Lehmann, J, Nagy JI, Atmadja S, Fibiger HC (1980) The nucleus basalis magnocellularis: the origin of a cholinergic projection to the neocortex of the rat. Neurosci 5:1161–1174Google Scholar
  21. Levi-Montalcini R (1982) Developmental neurobiology and the natural history of nerve growth factor. Ann Rev Neurosci 5:341–362Google Scholar
  22. Lindsay RM (1979) Adult rat brain astrocytes support survival of both NGF-dependent and NGF-insensitive neurons. Nature 282:80–82Google Scholar
  23. Loy R, Moore RY (1977) Anomalous innervation of the hippocampal formation by peripheral sympathetic axons following mechanical injury. Exp Neurol 57:645–650Google Scholar
  24. Loy R, Milner TA, Moore RY (1980) Sprouting of sympathetic axons in the hippocampal formation: conditions necessary to elicit ingrowth. Exp Neurol 67:349–411Google Scholar
  25. Mobley WC, Rutkowski IL, Tennekoon GL, Buchanan K, Johnston M V (1985) Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor. Science 229:284–287Google Scholar
  26. Otten U, Weskamp G, Schlumpf M, Lichtensteiger W, Mobley WC (1985) Effects of antibodies against nerve growth factor on developing cholinergic forebrain neurons in the rat. Soc Neurosci Abst 11:661Google Scholar
  27. Schwab ME, Otten U, Agid Y, Thoenen H (1979) NGF in the rat CNS: absence of specific retrograde axonal transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra. Brain Res 168:473–483Google Scholar
  28. Seiler A, Schwab ME (1984) Specific retrograde transport of nerve growth factor from neocortex to nucleus basalis in the rat. Brain Res 300:33–39Google Scholar
  29. Shelton DL, Reichardt LF (1984) Expression of theβ-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs. Proc Natl Acad Sci USA 81:7951–7955Google Scholar
  30. Springer J, Tayrien M, Koh S, Loy R (1986) Increased NGF immunoreactivity in hippocampal astrocytes following fimbria lesion. The Anat Record 214:127AGoogle Scholar
  31. Stenevi U, Björklund A (1978) Growth of vascular sympathetic axons into the hippocampus after lesions of the septo-hippocampal pathway: a pitfall in brain lesion studies. Neurosci Lett 7:219–224Google Scholar
  32. Taniuchi M, Schweitzer JB, Johnson EM (1986) Nerve growth factor receptor molecules in rat brain. Proc Natl Acad Sci USA 83:1950–1954Google Scholar
  33. Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand Suppl 367:1–48Google Scholar
  34. Wenk GL, Olton DS (1984) Recovery of neocortical choline acetyltransferase activity following ibotenic acid injection into the nucleus basalis of Meynert in rats. Brain Res 293:184–186Google Scholar
  35. Weskamp G, Otten U (1986) An enzyme-linked immunoassay for nerve growth factor (NGF): a tool for studying regulatory mechanisms involved in NGF production in brain and in pe-ripheral tissues. J Neurochem (in press)Google Scholar
  36. Weskamp G, Lorez HP, Otten U (1985) Development of a highly sensitive immunoassay for measurement of endogenous nerve growth factor in peripheral and central nervous system of the adult rat. Soc Neurosci Abst 11:940Google Scholar
  37. Weskamp G, Gasser UE, Dravid AR, Otten U (1986) Fimbriafornix lesion increases nerve growth factor content in adult rat septum and hippocampus. Neurosci Lett 70:121–126Google Scholar
  38. Yankner BA, Shooter EM (1982) The biology and mechanism of action of nerve growth factor. Ann Rev Biochem 51:845–868Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • G. Weskamp
    • 1
  • H. P. Lorez
    • 2
  • H. H. Keller
    • 2
  • U. Otten
    • 1
  1. 1.Department of PharmacologyBiocenter of the UniversityBaselSwitzerland
  2. 2.Pharmaceutical Research DepartmentF. Hoffmann-La Roche & Co., Ltd.BaselSwitzerland

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