Experimental Brain Research

, Volume 101, Issue 2, pp 291–296 | Cite as

Platelet-derived growth factor exerts trophic effects on rat striatal DARPP-32-containing neurons in culture

  • N. Nakao
  • P. Brundin
  • K. Funa
  • O. Lindvall
  • P. Odin
Original Paper


The objective of the present study was to determine if either of the two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, exerts trophic effects in vitro on developing rat striatal neurons. Striatal neurons were identified using immunocytochemistry for dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). In control cultures without PDGF, the mean number of DARPP-32-positive neurons decreased by 47% at days 3 to 5 in vitro. PDGF-BB, but not PDGF-AA, significantly increased the number of DARPP-32-positive neurons both at day 3 (by 42%) and day 5 (by 149%). Total cell number was similar in control and PDGF BB-treated cultures, suggesting that, in striatal cultures, the action of PDGF-BB is relatively specific for DARPP-32-positive neurons. The DARPP-32-positive neurons in PDGF-BB-treated cultures had longer neurites and larger soma areas than those in control and in PDGF-AA-treated cultures. Our data provide evidence that PDGF-BB exerts a trophic action on striatal DARPP-32-positive neurons in vitro by promoting cell survival and morphological differentiation, although a stimulatory effect on intraneuronal DARPP-32 levels also is possible. The findings raise the possibility that PDGF-BB might also be involved in the development and maintenance of striatal neurons in vivo, and could be used to counteract striatal degeneration in models of Huntington's disease.

Key words

Platelet-derived growth factor Striatal neurons DARPP-32 Huntington's disease Rat 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bayer SA (1984) Neurogenesis in the rat neostriatum. Int J Dev Neurosci 2:163–175CrossRefGoogle Scholar
  2. Bottenstein P, Sato GH (1979) Growth of a rat neuroblastoma cell line in serum-free supplement medium. Proc Natl Acad Sci USA 76:514–517CrossRefGoogle Scholar
  3. 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 133:140–147CrossRefGoogle Scholar
  4. Foster GA, Schultzberg M, Hökfelt T, Goldstein M, Hemmings HC, Ouimet CC, Walaas SI, Greengard P (1987) Development of dopamine- and cyclic adenosine-3':5'-monophosphate-regulated phosphoprotein (DARPP-32) in the prenatal rat central nervous system, and its relationship to the arrival of presumptive dopaminergic innervation. J Neurosci 7:1994–2018CrossRefGoogle Scholar
  5. Freese A, Finklestein SP, DiFiglia M (1992) Basic fibroblast growth factor protects striatal neurons in vitro from NMDA-receptor mediated excitotoxicity. Brain Res 575:351–355CrossRefGoogle Scholar
  6. Frim DM, Uhler TA, Short MP, Ezzedine ZD, Klagsbrun M, Breakefield XO, Isacson O (1993) Effects of biologically delivered NGF, BDNF and bFGF on striatal excitotoxic lesions. Neuroreport 4:367–370CrossRefGoogle Scholar
  7. Giacobini MMJ, Almström S, Funa K, Olson L (1993) Differential effects of platelet-derived growth factor isoforms on dopamine neurons in vivo: -BB supports cell survival, -AA enhances fiber formation. Neuroscience 57:923–929CrossRefGoogle Scholar
  8. Graybiel AM and Ragsdale CW (1983) Biochemical anatomy of the striatum. In: Emson PC (ed) Chemical neuroanatomy. Raven Press, New York, pp 427–504Google Scholar
  9. Harper PS (1991) Huntington's disease. Major problem in neurology, vol 22. Saunders, LondonGoogle Scholar
  10. 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 240:1529–1531CrossRefGoogle Scholar
  11. Heldin C-H, Westermark B (1990) Platelet-derived growth factor: mechanism of action and possible in vivo function. Cell Regulation 1:555–566CrossRefGoogle Scholar
  12. Heldin C-H, Westermark B, Wasteson Å (1979) Platelet-derived growth factor: purification and partial characterization. Proc Natl Acad Sci USA 76:3722–3726CrossRefGoogle Scholar
  13. Heldin C-H, 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 7:1387–1393CrossRefGoogle Scholar
  14. Matsuda S, Saito H, Nishiyama N (1990) Effect of basic fibroblast growth factor on neurons cultured from various regions of postnatal rat brain. Brain Res 520:310–316CrossRefGoogle Scholar
  15. Nakao N, Odin P, Brundin P (1994) Selective sub-dissection of the striatal primordium for cultures affects the yield of DARPP-32-containing neurons. Neuroreport 5:1081–1084CrossRefGoogle Scholar
  16. Nikkhah G, Odin P, Smits A, Tingström A, Othberg A, Brundin P, Funa K, Lindvall O (1993) Platelet-derived growth factor promotes survival of rat and human mesencephalic dopaminergic neurons in culture. Exp Brain Res 92:516–523CrossRefGoogle Scholar
  17. Noble M, Murray K, Stooban P, Waterfield MD, Riddle P (1988) Platelet-derived growth factor promotes division and mobility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature 333:560–565CrossRefGoogle Scholar
  18. 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 1:271–281CrossRefGoogle Scholar
  19. Ouimet CC, Greengard P (1990) Distribution of DARPP-32 in the basal ganglia: an electron microscopic study. J Neurocytol 19:39–52CrossRefGoogle Scholar
  20. Ouimet CC, Miller PE, Hemmings Jr. HC, Walaas SI, Greengard P (1984) DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization. J Neurosci 4:111–124CrossRefGoogle Scholar
  21. Pringle NP, Mudhar HS, Collarini EJ, Richardson WD (1992) PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage. Development 115:535–551PubMedGoogle Scholar
  22. Raff MC, Lillien LE, Richardson WD, Burne JF, Noble MD (1988) Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature 333:562–565CrossRefGoogle Scholar
  23. Reddy UR, Pleasure D (1992) Expression of platelet-derived growth factor (PDGF) and PDGF receptor genes in the developing rat brain. J Neurosci Res 31:670–677CrossRefGoogle Scholar
  24. 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 64:217–227CrossRefGoogle Scholar
  25. Schumacher JM, Short MP, Hyman BT, Breakefield XO, Isacson O (1991) Intracerebral implantation of nerve growth factor-producing fibroblasts protects striatum against neurotoxic levels of excitatory amino acids. Neuroscience 45:561–570CrossRefGoogle Scholar
  26. Smart IHM and Sturrock RR (1979) Ontogeny of the neostriatum. In: Divac I, Öberg RGE (eds) The neostriatum. Pergamon Press, Oxford, pp 127–146CrossRefGoogle Scholar
  27. 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 88:8159–8163CrossRefGoogle Scholar
  28. Smits A, Ballagi AE, Funa K (1993) PDGF-BB exerts trophic activity on cultured GABA interneurons from the newborn rat cerebellum. Eur J Neurosci 5:986–994CrossRefGoogle Scholar
  29. The Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:971–983CrossRefGoogle Scholar
  30. Ventimiglia R, Mather P, Lindsay RM (1993) Brain-derived neurotrophic factor promotes survival and biochemical and morphological differentiation of striatal GABA neurons in vitro. Soc Neurosci Abstr 19:666Google Scholar
  31. Walicke PA (1988) Basic and acidic fibroblast growth factors have trophic effects on neurons from multiple CNS regions. J Neurosci 8:2618–2627CrossRefGoogle Scholar
  32. 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 64:209–216CrossRefGoogle Scholar
  33. Zhou D, DiFiglia M (1993) Basic fibroblast growth factor enhances the growth of postnatal neostriatal GABAergic neurons in vitro. Exp Neurol 122:171–188CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • N. Nakao
    • 1
    • 2
  • P. Brundin
    • 1
  • K. Funa
    • 3
  • O. Lindvall
    • 1
  • P. Odin
    • 1
  1. 1.Restorative Neurology Unit, Department of NeurologyUniversity HospitalLundSweden
  2. 2.Department of Neurological SurgeryWakayama Medical CollegeWakayama CityJapan
  3. 3.Biomedical CentreLudwig Institute for Cancer ResearchUppsalaSweden

Personalised recommendations