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The Neuronotrophic Hypothesis of the Aging Brain

  • M. G. Nunzi
  • G. Toffano
Conference paper
Part of the NATO ASI Series book series (volume 9)

Abstract

Aging in the central nervous system (CNS) and age-related neuropathological conditions is known to be characterized by a deficit in specific neurotransmission systems, due to vulnerability of selective populations of neurons. Nevertheless, pharmacological strategies aimed at reducing or halting the progression of neurodegenerative disorders have led to minor therapeutic efficacy. As far as Alzheimer’s disease is concerned, cholinomimetic agents have not yet proven to be reliably effective (Rossor, 1982), and dopaminergic agonist administration for Parkinson’s disease has proven unable to prevent degeneration of the nigro-striatal projections (Hefti and Melamed, 1980). Lack of knowledge of both the etiology and pathogenetic mechanisms underlying neuronal degeneration, has hampered further development of therapies. However, the progress achieved in recent years in the field of basic and applied neuroscience has offered significant clues for exploring new therapeutic avenues.

Keywords

Amyotrophic Lateral Sclerosis Nerve Growth Factor Tyrosine Hydroxylase Adult Central Nervous System Trophic Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Appel S H (1981) A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism and Alzheimer’s disease. Ann Neurol 10: 499–505.PubMedCrossRefGoogle Scholar
  2. Bjorklund A and Stenevi U (1981) In vivo evidence for a hippocampal adrenergic neuronotrophic factor specifically released on septal deafferentiation. Brain Res 229: 403–428.PubMedCrossRefGoogle Scholar
  3. Dal Toso R, Giorgi D, Presti D, Benvegnu D, Favaron M, Soranzo C, Leon A. and Toffano G (1986) Neuronotrophic activity for CNS neurons extracted from bovine caudate nucleus: partial purification and characterization. In: R. Levi Montalcini (ed) Molecular Aspects of Neurobiology, Springer-Verlag, Berlin pp. 198–201.CrossRefGoogle Scholar
  4. Dal Toso R, Presti D, Benvegnu D, Giorgi 0, Vicini S, Azzone G F, Toffano G and Leon A. Development of phenotypic traits and survival of neurons in dissociated fetal mesencephalic serum-free cell cultures: effects of cell density and stimulation by adult mammalian brain extract. J Neurosci (submitted)Google Scholar
  5. Ebendal T, Olson L, Seiger A and Hedlund K O (1980) Nerve growth factors in the rat iris. Nature 286: 25–28.PubMedCrossRefGoogle Scholar
  6. Frotscher M and Leranth C (1985) Cholinergic innervation of the rat hippocampus as revealed by choline acetyl-transferase immunocytochemistry: a combined light and electronmicroscopic study. J Comp Neurol 239: 237–246.PubMedCrossRefGoogle Scholar
  7. Gage F M, Bjorklund A and Stenevi U (1984) Denervation releases a neuronal survival factor in adult rat hippocampus. Nature 308: 637–639.PubMedCrossRefGoogle Scholar
  8. Geddes J W, Mananghan D T and Cotman C W (1985) Plasticity of hippocampal circuity in Alzheimer’s disease. Science 230: 1179–1181.PubMedCrossRefGoogle Scholar
  9. Gurney M E (1984) Suppression of sprouting at the neuromuscular junction by immune sera. Nature 307: 456–548.CrossRefGoogle Scholar
  10. Gurney M E, Balton A C, Casham N and Antel J P (1984) Inhibition of terminal axonal sprouting by serum from patients with amyotrophic lateral sclerosis. New Engl J Med 311: 933–939.PubMedCrossRefGoogle Scholar
  11. Hornykiewicz O (1983) Parkinson’s disease and the aging basal ganglia. In: Gipsen WH, Traber J (eds) Aging in the Brain. Elsevier Science Publisher, London, Vol. 7, pp 553 - 260.Google Scholar
  12. Hefti F and Melamed E (1980) L-DOPA’s mechanisms of action in Parkinson’s disease. TINS 3: 229–231.Google Scholar
  13. Korsching S, Auburger G, Neumann R, Scott J and Thoenen H (1985) Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J 4: 1389–1393.PubMedGoogle Scholar
  14. Lippa A S, Critchett D J, Ehlert F, Yamamura H I, Enna S J and Bartus R T (1981) Age-related alterations in neurotransmitter receptors: an electrophysiological and biochemical analysis. Neurobiol Aging 2: 3–8.PubMedCrossRefGoogle Scholar
  15. Manthorpe M, Luyten W, Longo F M and Varon S (1983) Endogenous and exogenous factors support neuronal survival and CAT activity in embryonic spinal cord cultures. Brain Res 267: 57–66.PubMedCrossRefGoogle Scholar
  16. Milan F, Nunzi M G, Guidolin D, Calderini G and Toffano G (1986) Age-related loss of dendritic spines in rat hippocampus: effect of phosphatidylserine administration. In: Bes A, Cahn J, Cahn R, Hoyer S, Marc-Vergues J P, Wiesniewski H M (eds) Senile Dementias: Early Detection. John Libbey Eurotext, London-Paris pp. 408–414.Google Scholar
  17. Nieto-Sampedro M, Lewis E R, Cotman C W, Manthorpe M, Skaper S D, Barbin G, Longo F M and Varon S (1982) Brain injury causes a time-dependent increase in neuronotrophic activity at the lesion site. Science 217: 860–861.PubMedCrossRefGoogle Scholar
  18. Nieto-Sampedro M, Manthorpe M, Barbin G, Varon S and Cotman CW (1983) Injury-induced neuronotrophic activity in adult rat brain. Correlation with survival of delayed inplants in a wound cavity. J Neurosci 3: 2219–2229.Google Scholar
  19. Rossor M. N. (1982) Neurotransmitters and CNS diseases dementia. Lancet 2: 1200–1204.PubMedCrossRefGoogle Scholar
  20. Thoenen H and Barde Y A (1980) Physiology of nerve growth factor. Physiol Reviews 60: 1284–1335.Google Scholar
  21. Varon S and Somjen G (1979) Neuron-Glia Interactions. Neurosci Res Prog Bull 17: 1–239.Google Scholar
  22. Varon S and Adler R (1981) Trophic and specifying factors directed to neuronal cells. Adv Cell Neurobiol 2: 115–163.Google Scholar
  23. Varon S (1985) Factors promoting the growth of the nervous system. Discussion in Neuroscience, FESN (Foundation for the study of the Nervous Systems), Vol. II, No. 3, pp. 1–62.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • M. G. Nunzi
    • 1
  • G. Toffano
    • 1
  1. 1.Fidia Neurobiological Research LaboratoriesAbano TermeItaly

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