Skip to main content
Log in

Platelet-derived growth factor promotes survival of rat and human mesencephalic dopaminergic neurons in culture

  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Summary

The effect of two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, was tested on dissociated cell cultures of ventral mesencephalon from rat and human embryos. PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase- (TH)-positive neurons in rat and human cell cultures. The mean number of TH-positive cells in the PDGF-BB-treated rat culture was 64% and 106% higher than in the control cultures after 7 and 10 days in vitro, respectively. Corresponding figures for human TH-positive neurons were 90% and 145%. The influence of PDGF-BB was specific for TH-positive neurons and not a general trophic effect, since no change of either total cell number or metabolic activity was found. In PDGF-BB-treated cultures of human but not rat tissue the TH-positive neurons had longer neurites than observed in control or PDGF-AA-treated cultures. These data indicate that PDGF-BB may act as a trophic factor for mesencephalic dopaminergic neurons and suggest that administration of PDGF-BB could ameliorate degeneration and possibly promote axonal sprouting of these neurons in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Appel SH (1982) Neurotrophic factors and diseases of aging: an approach to ALS, parkinsonism, and Alzheimer's disease. In: Comparative pathobiology of major age-related diseases, current status and research frontiers. Liss, New York, pp 411–423

    Google Scholar 

  • Bottenstein P, Sato GH (1979) Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci USA 76:514–517

    Google Scholar 

  • Date I, Notter MFD, Felten SY, Felten DL (1990) MPTP-treated young mice but not aging mice show partial recovery of the nigrostriatal dopaminergic system by stereotaxic injection of acidic fibroblast growth factor (aFGF). Brain Res 526:156–160

    Google Scholar 

  • Engele J, Bohn MC (1991) The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia. J Neurosci 11:3070–3078

    Google Scholar 

  • Ferrari G, Minozzi M-C, Toffano G, Leon A, Skaper SD (1989) Basic fibroblast growth factor promotes the survival and development of mesencephalic neurons in culture. Dev Biol 133:140–147

    Google Scholar 

  • Hart CE, Forstrom JW, Kelly JD, Seifert RA, Smith RA, Ross R, Murray MJ, Bowen-Pope DF (1988) Two classes of PDGF receptor recognize different isoforms of PDGF. Science 240(10):1529–1531

    Google Scholar 

  • Heldin C-M, Westermark B (1990) Platelet-derived growth factor: mechanism of action and possible in vivo function. Cell Regul 1:555–566

    Google Scholar 

  • Heldin C-M, Bäckström G, Östman A, Hammacher A Rönnstrand L, Rubin K, Nistér M, Westermark B (1988) Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types. EMBO J: 1387–1393

  • Hyman C, Hofer M, Barde Y-A, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350:230–232

    Article  CAS  PubMed  Google Scholar 

  • Knüsel B, Michel PP, Schwaber SS, Hefti F (1990) Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. J Neurosci 10:558–570

    CAS  PubMed  Google Scholar 

  • Knüsel B, Winslow JW, Rosenthal A, Burton LE, Seid DP, Nikolics K, Hefti F (1991) Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3. Proc Natl Acad Sci USA 88:961–965

    Google Scholar 

  • Lindvall O, Widner H, Rehncrona S, Brundin P, Odin P, Gustavii B, Frackowiak R, Leenders KL, Sawle G, Rothwell JC, Björklund A, Marsden CD (1992) Transplantation of fetal dopamine neurons in Parkinson's disease: one-year clinical and neurophysiological observations in two patients with putaminal implants. Ann Neurol 31:155–165

    Google Scholar 

  • Manthorpe M, Fagini R, Skaper SD, Varon S (1986) An automatic colorimetric microassay for neurotrophic factors. Brain Res Dev Brain Res 25:191–198

    Google Scholar 

  • Nikkhah G, Tonn JC, Hoffmann O, Kraemer HP, Darling JL, Schönmayr R, Schachenmayr W (1992) The MTT assay for chemosensitivity testing of human tumors of the central nervous system. J Neurooncol 13:297–307

    Google Scholar 

  • Östman A, Bäckström G, Fong N, Betsholtz C, Wernstedt C, Hellman U, Westermark B, Valenzuela P, Heldin C-H (1989) Expression of three recombinant homodimeric isoforms of PDGF in Saccharomyces cerevisiae: evidence for difference in receptor binding and functional activities. Growth Factors 1:271–281

    Google Scholar 

  • Otto D, Unsicker K (1990) Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice. J Neurosci 10 (6):1912–1921

    CAS  PubMed  Google Scholar 

  • Pringle NP, Mudhar HS, Collarini EJ, Richardson WD (1992) PDGF receptors in the rat CNS: during late neurogenesis, PDGF α-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage. Development (in press)

  • Raines EW, Bowen-Pope DF, Ross R (1990) Peptide growth factors and their receptors. In: Sporn MB, Roberts AB (eds) Handbook of experimental pharmacology, vol 95/I. Springer, Berlin Heidelberg 95:1, pp 173–262

    Google Scholar 

  • Reddy UR, Pleasure D (1992) Expression of platelet-derived growth factor (PDGF) and PDGF receptor genes in the developing rat brain. J Neurosci Res 31:670–677

    Google Scholar 

  • Richardson WD (1991) PDGF in neurons. Curr Biol 1:162–164

    Google Scholar 

  • Sasahara M, Fries JWU, Raines EW, Gown AM, Westrum LE, Frosch MP, Bonthron DT, Ross R, Collins T (1991) PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model. Cell 64:217–227

    Google Scholar 

  • Sauer H, Fischer W, Nikkhah G, Brundin P, Björklund A (1992) Brain-derived neurotrophic factor enhances function rather than the survival of intrastriatal mesencephalic grafts (abstract). 15th Annual Meeting of the European Neuroscience Association, Munich, Germany

  • Smits A, Kato M, Westermark B, Nistér M, Heldin C-H, Funa K (1991) Neurotrophic activity of platelet-derived growth factor (PDGF): rat neuronal cells possess functional PDGF β -type receptors and respond to PDGF. Proc Natl Acad Sci USA 88:8159–8163

    Google Scholar 

  • Steinbusch HW, Vermeulen RJ, Tonnaer JA (1990) Basic fibroblast growth factor enhances survival and sprouting of fetal dopaminergic cells implanted in the denervated rat caudate-putamen: preliminary observations. Prog Brain Res 82:81–86

    Google Scholar 

  • Yeh H-J, Rult KG, Wang Y-X, Parks WC, Snider WD, Duel TF (1991) PDGF A-chain gene is expressed by mammalian neurons during development and in maturity. Cell 64:209–216

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nikkhah, G., Odin, P., Smits, A. et al. Platelet-derived growth factor promotes survival of rat and human mesencephalic dopaminergic neurons in culture. Exp Brain Res 92, 516–523 (1993). https://doi.org/10.1007/BF00229041

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00229041

Key words

Navigation