A Striatal-Derived DA Neuron Growth Factor: Implication in Parkinson’s Disease
The anti-Parkinsonian efficacy of adrenal medulla-to-brain transplantation was initially thought to result from increased dopamine (DA) secretion from the implanted chromaffin cells. However, examination of the CSF from transplant recipients, failed to demonstrate increased levels of DA despite clinical improvement.1 This would suggest that mechanisms other than increased DA secretion may be responsible for the therapeutic benefits resulting from medulla transplantation. Any alternative hypothesis advanced must consider recent observations suggesting that: 1- endogenous DA tone appears increased by medulla transplantation,3 2- transplantatiort leads to enhanced sprouting of tyrosine hydroxylase positive f hers,6 and 3- transplantation results in bilateral clinical improvement.5 The release of a neuro-trophic-factor (NTF) capable of diffusing through CSF is consistent with these observations.
KeywordsNerve Growth Factor Tyrosine Hydroxylase Neuron Growth Striatal Tissue AMPH Treatment
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- 1.P. M. Carvey, J.S. Kroin, T.J. Zhang, T.M. O’Dorisio, T.L. Yaksch, A. McRae, A. Dahlstrom, L.C. Kao, C.G. Goetz, C.M. Tanner, K.M. Shannon, and H.L. Klawans, Biochemical and immunochemical characterization of ventricular CSF from Parkinson’s disease patients with adrenal medulla transplants. Neurology (Suppl. 1 ) 38: 144 (1988).Google Scholar
- 2.P. M. Carvey, L.R. Ptak, L.C. Kao, and H.L. Klawans, Striate’ homogenates from animals chronically treated with haloperidol stimulate dopamine and GABA uptake in rostral mesencephalic tegmental cultures. Clin. Neuropharm. In Press 1989.Google Scholar
- 4.D. M. Gash, J.H. Kordower, M.S. Fiandanca, S.H. Okawara, S.S. Jiao, M.F.D. Notter, and J.T. Hansen. Adrenal medullary autographs in nonhuman primates: regeneration and sprouting of host dopaminergic systems. Soc. Neurosci. Abstr. 14 (l): 735 (1988).Google Scholar
- 5.C. G. Goetz, C. Olanow, W.C. Koller, R.D. Penn, D. Cahill, R. Morantz, G. Stebbins, C.M. Tanner, H.L. Klawans, K.M. Shannon, C.L. Comella, T. Witt, C. Cox, M. Waxman, and L. Gauger. Multicenter study of adrenal medullary transplant to the striatum of patients with advanced Parkinson’s disease. N. Engl. J. Med. 320: 337–41 (1989).Google Scholar
- 6.A. Heller, P.C. Hoffman, C. Kotake, and I. Shalaby. Regulation of biochemical differentiation of embryonic dopamine neurons in vitro. Psychopharm. Bull. 19: 311–316 (1983).Google Scholar
- 7.F. Hefti, B. Knusel, P.P. Michel, E.O. Junard, B.R. Due, and J.S. Schwaber. NGF and injured Cholinergic Neurons. Presented at Trophic Factors and the Nervous System. American Soc. Neurochem. 20th Ann. Satellite Meeting, Columbus, Ohio. 1989.Google Scholar
- 9.K. Steece-Collier, T.J. Collier, C.D. Sladek, and J.R. Sladek Jr. Chronic levodopa treatment decreases the viability of grafted and cultured embryonic rat mesencephalon dopamine neurons. Soc. Neurosci. Abstr. 15, 2: 1354 (1989).Google Scholar