title: Beneficial effects of intraventricularly administered BMP-7 following a striatal 6-hydroxydopamine lesion.
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-beta (TGF-beta) 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.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Zuch
authors.forename: Daniel
authors.initials: D
authors.lastname: David
authors.forename: Livia
authors.initials: L
authors.lastname: Ujhelyi
authors.forename: John L
authors.initials: JL
authors.lastname: Hudson
authors.forename: Greg A
authors.initials: GA
authors.lastname: Gerhardt
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kaplan
authors.forename: Paula C
authors.initials: PC
authors.lastname: Bickford
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D016627:Oxidopamine; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D009414:Nerve Growth Factors; D016212:Transforming Growth Factor beta; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine