Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged Parkinsonian rat

Gene Therapy volume 6, pages 1936–1951 (1999)Cite this article

Abstract

Injection of an adenoviral (Ad) vector encoding human glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic (DA) neurons in the substantia nigra (SN) of young rats. As Parkinson’s disease occurs primarily in aged populations, we examined whether chronic biosynthesis of GDNF, achieved by adenovirus-mediated delivery of a GDNF gene (AdGDNF), can protect DA neurons and improve DA-dependent behavioral function in aged (20 months) rats with progressive 6-OHDA lesions of the nigrostriatal projection. Furthermore, the differential effects of injecting AdGDNF either near DA cell bodies in the SN or at DA terminals in the striatum were compared. AdGDNF or control vector was injected unilaterally into either the striatum or SN. One week later, rats received a unilateral intrastriatal injection of 6-OHDA on the same side as the vector injection. AdGDNF injection into either the striatum or SN significantly reduced the loss of FG labelled DA neurons 5 weeks after lesion (P ⩽ 0.05). However, only striatal injections of AdGDNF protected against the development of behavioral deficits characteristic of unilateral DA depletion. Striatal AdGDNF injections also reduced tyrosine hydroxylase fiber loss and increased amphetamine-induced striatal Fos expression. These results demonstrate that increased levels of striatal, but not nigral, GDNF biosynthesis prevents DA neuronal loss and protects DA terminals from 6-OHDA-induced damage, thereby maintaining DA function in the aged rat.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  1. Bohn MC, Choi-Lundberg DL . Neurotrophic factor gene therapy for neurodegenerative disease Gene Ther Molec Biol 1998 1: 265–277

    Google Scholar 

  2. Choi-Lundberg DL, Bohn MC . Applications of gene therapy to neurological diseases and injuries. In: Quesenberry PJ, Stein GS, Forget B, Weissman S (eds) . Stem Cell Biology and Gene Therapy Wiley-Liss: New York 1998 503–553

    Google Scholar 

  3. Connor B, Dragunow M . The role of neuronal growth factors in neurodegenerative disorders of the human brain Brain Res 1998 27: 1–39

    Article  CAS  Google Scholar 

  4. Lindsay RM . Neurotrophic growth factors and neurodegenerative diseases: therapeutic potential of the neurotrophins and ciliary neurotrophic factor Neurobiol Aging 1994 15: 249–251

    Article  CAS  PubMed  Google Scholar 

  5. Bohn MC, Choi-Lundberg DL . Gene therapies for Parkinson’s disease. In: Chiocca EA, Breakfield XO (eds) . Gene Therapy for Neurological Disorders and Brain Tumors Humana Press: Totowa, NJ 1997 377–395

    Google Scholar 

  6. Unsicker K . GDNF: a cytokine at the interface of TGF-betas and neurotrophins Cell Tiss Res 1996 286: 175–178

    Article  CAS  Google Scholar 

  7. Krieglstein K, Suter-Crazzolara C, Unsicker K . Development of mesencephalic dopaminergic neurons and the transforming growth factor-beta superfamily J Neural Transmis Suppl 1995 46: 209–216

    CAS  Google Scholar 

  8. Lin L-FH et al. A glial cell-line derived neurotrophic factor for midbrain dopaminergic neurons Science 1993 260: 1130–1132

    Article  CAS  PubMed  Google Scholar 

  9. Beck KD et al. Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain Nature 1995 373: 339–341

    Article  CAS  PubMed  Google Scholar 

  10. Hoffer BJ et al. Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo Neurosci Lett 1994 182: 107–111

    Article  CAS  PubMed  Google Scholar 

  11. Kearns C, Gash D . GDNF protects nigral dopaminergic neurons against 6-hydroxydopamine in vivo Brain Res 1995 672: 104–111

    Article  CAS  PubMed  Google Scholar 

  12. Tomac A et al. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo Nature 1995 373: 335–339

    Article  CAS  PubMed  Google Scholar 

  13. Sauer H, Rosenblad C, Bjorklund A . Glial cell line-derived neurotrophic factor but not transforming growth factor beta-3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion Proc Nat Acad Sci USA 1995 92: 8935–8939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bowenkamp KE et al. Glial cell line-derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons J Comp Neurol 1995 355: 479–489

    Article  CAS  PubMed  Google Scholar 

  15. Lapchak PA, Miller PJ, Collins F, Jiao S . Glial cell line-derived neurotrophic factor attenuates behavioral deficits and regulates nigrostriatal dopaminergic and peptidergic markers in 6-hydroxydopamine-lesioned adult rats: comparison of intraventricular and intranigral delivery Neuroscience 1997 78: 61–72

    Article  CAS  PubMed  Google Scholar 

  16. Rosenblad C, Martinez-Serrano A, Bjorklund A . Intrastriatal glial cell line-derived neurotrophic factor promotes sprouting of spared nigrostriatal dopaminergic afferents and induces recovery of function in a rat model of Parkinson’s disease Neuroscience 1998 82: 129–137

    Article  CAS  PubMed  Google Scholar 

  17. Lindner MD et al. Implantation of encapsulated catecholamine and GDNF-producing cells in rats with unilateral dopamine deletions and Parkinsonian symptoms Exp Neurol 1995 132: 62–76

    Article  CAS  PubMed  Google Scholar 

  18. Gash DM et al. Functional recovery in Parkinsonian monkeys treated with GDNF Nature 1996 380: 252–255

    Article  CAS  PubMed  Google Scholar 

  19. Ghodsi A et al. Extensive beta-glucuronidase activity in murine central nervous system after adenovirus-mediated gene transfer to brain Hum Gene Ther 1998 9: 2331–2340

    Article  CAS  PubMed  Google Scholar 

  20. Akli S et al. Transfer of a foreign gene into the brain using adenovirus vectors Nat Genet 1993 3: 224–228

    Article  CAS  PubMed  Google Scholar 

  21. Bajocchi G, Feldman SH, Crystal RG, Mastrangeli A . Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors Nat Genet 1993 3: 229–234

    Article  CAS  PubMed  Google Scholar 

  22. Davidson BL et al. A model system for in vivo gene transfer into the central nervous system using an adenovirus vector Nat Genet 1993 3: 219–223

    Article  CAS  PubMed  Google Scholar 

  23. Le Gal La Salle G et al. An adenovirus vector for gene transfer into neurons and glia in the brain Science 1993 259: 988–990

    Article  CAS  PubMed  Google Scholar 

  24. Choi-Lundberg DL et al. Dopaminergic neurons protected from degeneration by GDNF gene therapy Science 1997 275: 338–341

    Article  Google Scholar 

  25. Davidson BL, Bohn MC . Recombinant adenovirus: a gene transfer vector for study and treatment of CNS disease Exp Neurol 1997 144: 125–130

    Article  CAS  PubMed  Google Scholar 

  26. Horellou P, Sabate O, Buc-Caron M-H, Mallet J . Adenovirus-mediated gene transfer to the central nervous system for Parkinson’s disease Exp Neurol 1997 144: 131–138

    Article  CAS  PubMed  Google Scholar 

  27. Choi-Lundberg DL et al. Behavioral and cellular protection of rat dopaminergic neurons by an adenoviral vector encoding glial cell line-derived neurotrophic factor Exp Neurol 1998 154: 261–275

    Article  CAS  PubMed  Google Scholar 

  28. Bilang-Bleuel A et al. Intrastriatal injection of an adenoviral vector expressing glial cell-line derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson’s disease Proc Natl Acad Sci USA 1997 94: 8818–8823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mandel R, Spratt S, Snyder R, Leff S . Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson’s disease in rats Proc Natl Acad Sci 1997 94: 14083–14088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bowenkamp K, Lapchak P, Hoffer B, Bickford P . Glial cell line-derived neurotrophic factor reverses motor impairment in 16–17 month old rats Neurosci Lett 1996 211: 81–84

    Article  CAS  PubMed  Google Scholar 

  31. Hebert MA, Gerhardt GA . Behavioural and neurochemical effects of intranigral administration of glial cell line-derived neurotrophic factor on aged Fischer 344 rats J Pharmacol Exp Ther 1997 282: 760–768

    CAS  PubMed  Google Scholar 

  32. Lapchak P, Miller P, Jiao S . Glial cell line-derived neurotrophic factor induces the dopaminergic and cholinergic phenotype and increases locomotor activity in aged Fischer-344 rats Neuroscience 1997 77: 745–752

    Article  CAS  PubMed  Google Scholar 

  33. Emerich DF et al. Alleviation of behavioral deficits in aged rodents following implantation of encapsulated GDNF-producing fibroblasts Brain Res 1996 736: 99–110

    Article  CAS  PubMed  Google Scholar 

  34. Date I et al. GDNF administration induces recovery of the nigrostriatal dopaminergic system both in young and aged parkinsonian mice NeuroReport 1998 9: 2365–2369

    Article  CAS  PubMed  Google Scholar 

  35. Zigmond M et al. Compensatory responses to partial loss of dopaminergic neurons: studies with 6-hydroxydopamine. In: Schneider J, Gupta M (eds) Current Concepts in Parkinson’s Disease Research Hogrefe and Huber: Göttingen 1993 pp 99–140

    Google Scholar 

  36. Demarest KT, Riegle GD, Moore KE . Characteristics of dopaminergic neurons in the aged male rat Neuroendocrinology 1980 31: 222–227

    Article  CAS  PubMed  Google Scholar 

  37. Unnerstall JR, Long MM . Differential effects of the intraventricular administration of 6-hydroxydopamine on the induction of type II beta-tubulin and tyrosine hydroxylase mRNA in the locus coeruleus of the aging Fischer 344 rat J Comp Neurol 1996 364: 363–381

    Article  CAS  PubMed  Google Scholar 

  38. Schallert T . Aging-dependent emergence of sensorimotor dysfunction in rats recovered from dopamine sustained early in life. In: Joseph JA (ed) Central Determinants of Age-Related Decline in Motor Function Annals of New York Academy of Science: New York 1988 pp 108–119

    Google Scholar 

  39. Bjorklund A, Rosenblad C, Winkler C, Kirik D . Studies on neuroprotective and regenerative effects of GDNF in a partial lesion model of Parkinson’s disease Neurobiol Dis 1997 4: 186–200

    Article  CAS  PubMed  Google Scholar 

  40. Ungerstedt U . Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behavior Acta Physiol Scand 1971 82: 49–68

    Article  Google Scholar 

  41. Sauer H, Oertel WH . Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine a combined retrograde tracing and immunocytochemical study in the rat Neuroscience 1994 59: 401–415

    Article  CAS  PubMed  Google Scholar 

  42. Liu FC, Graybiel AM, Dunnett SB, Braughman RW . Intrastriatal grafts derived from fetal striatal primordia. II. Reconstitution of cholinergic and dopaminergic systems J Comp Neurol 1990 295: 1–14

    Article  CAS  PubMed  Google Scholar 

  43. Morgan JI, Curran T . Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun Ann Rev Neurosci 1991 14: 421–451

    Article  CAS  PubMed  Google Scholar 

  44. Cenci M et al. Dopaminergic transplants normalize amphetamine and apomorphine-induced Fos expression in the 6-hydroxydopamine lesioned striatum Neuroscience 1992 46: 943–957

    Article  CAS  PubMed  Google Scholar 

  45. Labandeira-Garcia J et al. Time course of striatal changes induced by 6-hydroxydopamine lesion of the nigrostriatal pathway, as studied by combined evaluation of rotational behavior and striatal Fos expression Exp Brain Res 1996 108: 69–84

    Article  CAS  PubMed  Google Scholar 

  46. Robertson HA, Peterson MR, Murphy K, Robertson GS . D1-dopamine receptor agonists selectively activate striatal c-fos independent of rotational behavior Brain Res 1989 503: 346–349

    Article  CAS  PubMed  Google Scholar 

  47. Graybiel AM, Moratalla R, Robertson HA . Amphetamine and cocaine induces drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdivisions of the striatum Proc Natl Acad Sci USA 1990 87: 6912–6916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Robertson GS, Vincenty SR, Fibiger HC . D1 and D2 dopamine receptors differentially regulate c-fos exprssion in striatonigral and striatopallidal neurons Neuroscience 1992 49: 285–296

    Article  CAS  PubMed  Google Scholar 

  49. Paul ML, Graybiel AM, David JC, Robertson HA . D1-like and D2-like dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of Parkinson’s disease J Neurosci 1992 12: 3729–3742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Konradi C, Cole RL, Heckers S, Hyman SE . Amphetamine regulates gene expression in rat striatum via transcription factor CREB J Neurosci 1994 14: 5623–5634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Berretta S, Robertson HA, Graybiel AM . Dopamine and glutamine agonists stimulate neuron-specific expression of Fos-like protein in the striatum J Neurophysiol 1992 68: 767–777

    Article  CAS  PubMed  Google Scholar 

  52. Matheson CR et al. Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor for sensory neurons: comparison with the effects of the neurotrophins J Neurobiol 1997 32: 22–32

    Article  CAS  PubMed  Google Scholar 

  53. Byrnes AP, Rusby JE, Wood MJA, Charlton HM . Adenovirus gene transfer causes inflammation in the brain Neuroscience 1995 66: 1015–1024

    Article  CAS  PubMed  Google Scholar 

  54. Bohn MC et al. Adenoviral-mediated transgene expression in non-human primate brain Hum Gene Ther 1999 10: 1175–1184

    Article  CAS  PubMed  Google Scholar 

  55. Lawrence MS et al. Inflammatory responses and their impact on beta-galactosidase transgene expression following adenovirus vector delivery to the primate caudate nucleus Gene Therapy 1999 6: 1368–1379

    Article  CAS  PubMed  Google Scholar 

  56. Martin D et al. Intranigral or intrastriatal injections of GDNF – effects on monoamine levels and behavior in rats Euro J Pharmacol 1996 317: 247–256

    Article  CAS  Google Scholar 

  57. Lapchak P et al. Pharmacological activities of glial cell line-derived neurotrophic factor (GDNF): preclinical development and application to the treatment of Parkinson’s disease Exp Neurol 1997 145: 309–321

    Article  CAS  PubMed  Google Scholar 

  58. Morgan D, Finch C . Dopaminergic changes in the basal ganglia: a generalized phenomenon of aging in mammals Ann NY Acad Sci 1998 515: 145–160

    Article  Google Scholar 

  59. Felten D et al. Age-related decline in the dopaminergic nigrostriatal system: the oxidative hypothesis and protective strategies Ann Neurol 1992 32: S133–S136

    Article  PubMed  Google Scholar 

  60. Roth GS, Joseph JA . Cellular and molecular mechanisms of impaired dopaminergic function during aging Ann NY Acad Sci 1994 719: 129–135

    Article  CAS  PubMed  Google Scholar 

  61. Hubble JP . Aging and the basal ganglia Neurol Clin 1998 16: 649–657

    Article  CAS  PubMed  Google Scholar 

  62. Yu T et al. Expression of GDNF family receptor components during development: implications in the mechanisms of interaction J Neurosci 1998 18: 4684–4696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Trupp M, Belluardo N, Funakoshi H, Ibanez CF . Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS J Neurosci 1997 17: 3554–3567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Glazner GW, Mu X, Springer JE . Localization of glial cell line-derived neurotrophic factor receptor alpha and c-ret mRNA in rat central nervous system J Comp Neurol 1998 391: 42–49

    Article  CAS  PubMed  Google Scholar 

  65. Kirik D, Rosenblad C, Bjorklund A . Characterization of behavioral and neurodegeneration changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat Exp Neurol 1998 153: 259–277

    Article  Google Scholar 

  66. Shults CW, Kimber T, Martin D . Intrastriatal injection of GDNF attenuates the effects of 6-hydroxydopamine NeuroReport 1996 7: 627–631

    Article  CAS  PubMed  Google Scholar 

  67. Schwarting R, Huston J . The unilateral 6-hydroxydopamine lesion model in behavioral brain research analysis of functional deficits, recovery and treatments Prog Neurobiol 1996 50: 275–331

    Article  CAS  PubMed  Google Scholar 

  68. Brass CA, Glick SD . Sex difference in drug-induced rotation in two strains of rats Brain Res 1981 223: 229–234

    Article  CAS  PubMed  Google Scholar 

  69. Tillerson JL, Castro SL, Zigmond MJ, Schallert T . Motor rehabilitation of forelimb use in unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson’s disease Soc Neurosci Abstr 1998 24: 1720

    Google Scholar 

  70. Naldini L et al. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector Proc Natl Acad Sci USA 1996 93: 11382–11388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kafri T et al. Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors Nat Genet 1997 17: 314–317

    Article  CAS  PubMed  Google Scholar 

  72. Kaplitt MG et al. Long-term expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain Nat Genet 1994 8: 148–154

    Article  CAS  PubMed  Google Scholar 

  73. McCown TJ et al. Differential and persistent expression pattern of CNS gene transfer by an adeno-associated virus (AAV) vector Brain Res 1996 713: 99–107

    Article  CAS  PubMed  Google Scholar 

  74. Lo WD et al. Adeno-associated virus-mediated gene transfer to the brain: duration and modulation of expression Hum Gene Ther 1999 10: 201–213

    Article  CAS  PubMed  Google Scholar 

  75. Yang Y et al. Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis Nat Genet 1994 7: 362–369

    Article  CAS  PubMed  Google Scholar 

  76. Fang B et al. Lack of persistence of E1-recombinant adenoviral vectors containing a temperature-sensitive E2a mutation in immunocompetent mice and hemophilia B dogs Gene Therapy 1996 3: 217–222

    CAS  PubMed  Google Scholar 

  77. Amalfitano A, Chamberlain JS . Isolation and characterization of packaging cell lines that coexpress the adenovirus E1, DNA polymerase, and preterminal proteins: implications for gene therapy Gene Therapy 1997 4: 258–263

    Article  CAS  PubMed  Google Scholar 

  78. Amalfitano A, Begy CR, Chamberlain JS . Improved adenovirus packaging cell lines to support the growth of replication-defective gene-delivery vectors Proc Natl Acad Sci USA 1996 93: 3352–3356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Amalfitano A et al. Production and characterization of improved adenovirus vectors with E1, E2b and E3 genes deleted J Virol 1998 72: 926–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Crouzet J et al. Recombinational construction in Escherichia coli of infectious adenoviral genomes Proc Natl Acad Sci USA 1997 94: 1414–1419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Armentano D et al. Characterization of an adenovirus gene transfer vector containing an E4 deletion Hum Gene Ther 1995 6: 1343–1353

    Article  CAS  PubMed  Google Scholar 

  82. Armentano D et al. Effect of the E4 region on the persistence of transgene expression from adenovirus vectors J Virol 1997 71: 2408–2416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Parks RJ et al. A helper-dependent adenovirus vector system: removal of helper virus by cre-mediated excision of the viral packaging signal Proc Natl Acad Sci USA 1996 93: 13565–13570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kochanek S et al. A new adenoviral vector: replacement of all viral coding sequences with a 26 kb of DNA independently expressing both full-length dystrophin and beta-galactosidase Proc Natl Acad Sci USA 1996 93: 5731–5736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Fisher KJ et al. Recombinant adenovirus deleted of all viral genes for gene therapy therapy of cystic fibrosis Virology 1996 217: 11–22

    Article  CAS  PubMed  Google Scholar 

  86. Morsy MA et al. An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene Proc Natl Acad Sci USA 1998 95: 7866–7871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Schallert T, Jones TA, Norton DA . A clinically relevant unilateral rat model of Parkinsonian akinesia J Neural Transplant Plast 1992 3: 332–333

    Article  PubMed Central  Google Scholar 

  88. Schallert T, Lindner MD . Rescuing neurons from trans-synaptic degeneration after brain damage: helpful, harmful, or neutral in recovery of function? Can J Psychol 1990 44: 276–292

    Article  CAS  PubMed  Google Scholar 

  89. Jones TA, Schallert T . Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage Brain Res 1992 581: 156–160

    Article  CAS  PubMed  Google Scholar 

  90. Jones TA, Schallert T . Use-dependent growth of pyramidal neurons after neocortical damage J Neurosci 1994 14: 2140–2152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kozlowski DA, James DC, Schallert T . Use-dependent exaggeration of neuronal injury after unilateral sensorimotor cortex lesions J Neurosci 1996 16: 4776–4786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Coggeshall RE, Lekan HA . Methods for determining numbers of cells and synapses: a case for more uniform standards of review J Comp Neurol 1996 364: 6–15

    Article  CAS  PubMed  Google Scholar 

  93. Abercrombie M . Estimation of nuclear population from microtome sections Anat Rec 1946 94: 239–247

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by NIH grants NS31957 and HD33531, The Medical Research Institute Council of Children’s Memorial Hospital, the Carver Foundation and The National Parkinson Foundation Center of Excellence in Parkinson’s Disease at the University of Pittsburgh Seed Money Program partially funded by the Tuchman Foundation, Princeton, New Jersey. AdGDNF and AdmuGDNF were the generous gifts of Genetic Therapy Inc/Novartis. The authors thank Dr Cristina Backman for assistance with surgeries, Dr Pauline Chou for assistance with analysis of pathology and Mr Richard Anderson (University of Iowa, Gene Transfer Vector Core) for preparation of vector stocks. We also thank Drs James Surmeier and Derek Choi-Lundberg for critical reading of the manuscript. B Connor is the recipient of a New Zealand Neurological Foundation Post-Doctoral Fellowship.

Author information

Authors and Affiliations

  1. Department of Psychology, University of Texas, Austin, TX, USA

    B Connor, D A Kozlowski & M C Bohn

  2. Department of Pediatrics, Children’s Memorial Institute for Education and Research, Northwestern University Medical School, Chicago, IL, USA

    T Schallert & J L Tillerson

  3. Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA, USA

    B L Davidson

Authors
  1. B Connor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D A Kozlowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Schallert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J L Tillerson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B L Davidson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M C Bohn
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Connor, B., Kozlowski, D., Schallert, T. et al. Differential effects of glial cell line-derived neurotrophic factor (GDNF) in the striatum and substantia nigra of the aged Parkinsonian rat. Gene Ther 6, 1936–1951 (1999). https://doi.org/10.1038/sj.gt.3301033

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3301033

Keywords

This article is cited by

Search

Advanced search

Quick links