Beneficial effects of intraventricularly administered BMP-7 following a striatal 6-hydroxydopamine lesion

Christina L. Zuch, Daniel David, Livia Ujhelyi, John L. Hudson, Greg A. Gerhardt, Paul L. Kaplan, Paula C. Bickford

Research output: Contribution to journalArticlepeer-review

Abstract

The present study was undertaken to investigate the effects of bone morphogenetic protein-7 (BMP-7), also named osteogenic protein-1 (OP-1), on the progression of a striatal 6-hydroxydopamine (6-OHDA) lesion. BMP-7, a member of the transforming growth factor-β (TGF-β) superfamily of proteins, has been shown to have protective effects in other animal models of neuronal damage. In this study, male Fischer 344 rats received striatal 6-OHDA lesions followed 1 week later by an intraventricular dose of BMP-7. No significant effect of BMP-7 treatment on spontaneous locomotor activity was observed, however BMP-7 significantly increased the density of tyrosine hydroxylase (TH) immunoreactivity (TH-ir) in the substantia nigra (SN) pars compacta, in the lesioned hemisphere [31.7±5.2 (optical density (O.D.) arbitrary units) control vs. 50.2±4.3 O.D. BMP-7-treated; p<0.05]. Interestingly, BMP-7 significantly increased TH-ir in the SN of the non-lesioned hemisphere (pars reticulata: 14.8±1.19 O.D. control vs. 36±2.6 O.D. BMP-7-treated, p<0.05; pars compacta: 29.0±4.9 O.D. control vs. 64.4±6.9 O.D. BMP-7-treated, p<0.001). A significant increase in DA concentration in the contralateral, non-lesioned hemisphere was also noted (113.2 ng/g control vs. 198.2 ng/g BMP-7-treated, p<0.01). In contrast to other intraventricularly administered neurotrophic factors, BMP-7 was not associated with an increase in the sensitivity to pain. These results suggest that BMP-7 is able to act as a dopaminotrophic agent without unwanted side effects and as such may be a useful pharmacological tool in the treatment of Parkinson's disease in humans.

Original languageEnglish (US)
Pages (from-to)10-16
Number of pages7
JournalBrain Research
Volume1010
Issue number1-2
DOIs
StatePublished - Jun 4 2004

Keywords

  • 6-Hydroxydopamine
  • Bone morphogenetic protein-7
  • Degenerative disease: Parkinson's
  • Disorders of the nervous system
  • Dopamine
  • Neurodegeneration
  • Osteogenic protein-1
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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