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: Christina L Zuch, Daniel David, Livia Ujhelyi, John L Hudson, Greg A Gerhardt, Paul L Kaplan, Paula C Bickford
• Journal: Brain research (Brain Res) Vol. 1010 Issue 1-2 Pg. 10-6 (Jun 04 2004) ISSN: 0006-8993 [Print] Netherlands
• PMID: 15126112 (Publication Type: Journal Article)

Chemical References

• BMP7 protein, human
• Bmp7 protein, rat
• Bone Morphogenetic Protein 7
• Bone Morphogenetic Proteins
• Nerve Growth Factors
• Transforming Growth Factor beta
• Oxidopamine
• Tyrosine 3-Monooxygenase
• Dopamine

Topics

• Animals
• Bone Morphogenetic Protein 7
• Bone Morphogenetic Proteins (pharmacology, therapeutic use)
• Corpus Striatum (drug effects, metabolism, physiopathology)
• Disease Models, Animal
• Dopamine (metabolism)
• Dose-Response Relationship, Drug
• Immunohistochemistry
• Male
• Motor Activity (drug effects, physiology)
• Nerve Growth Factors (pharmacology, therapeutic use)
• Neurons (drug effects, enzymology)
• Oxidopamine
• Pain Threshold (drug effects, physiology)
• Parkinsonian Disorders (chemically induced, drug therapy, metabolism)
• Rats
• Rats, Inbred F344
• Substantia Nigra (drug effects, enzymology)
• Transforming Growth Factor beta (pharmacology, therapeutic use)
• Treatment Outcome
• Tyrosine 3-Monooxygenase (drug effects, metabolism)
• Up-Regulation (drug effects, physiology)