Neurotrophic effects of bone morphogenetic protein-7 in a rat model of Parkinson's disease.
Previous studies have demonstrated that pretreatment with bone morphogenetic protein-7 (BMP7) reduces ischemic neuronal injury in vivo. Moreover, exogenous application of BMP7 increases both the number of tyrosine hydroxylase (+) cells and dopamine (DA) uptake in rat mesencephalic cell cultures. The purpose of this study was to investigate the in vivo effects of BMP7 on 6-hydroxydopamine (6-OHDA) induced lesioning of midbrain DA neurons. Adult Fischer 344 rats were anesthetized and injected with BMP7 or vehicle into the left substantia nigra, followed by local administration of 9 microg of 6-OHDA into the left medial forebrain bundle. The lesioned animals that received BMP7 pretreatment, as compared to vehicle/6-OHDA controls, had a significant reduction in methamphetamine-induced rotation 1 month after the surgery. BMP7-pretreatment partially preserved KCl-induced dopamine release in the lesioned striatum and significantly increased TH immunoreactivity in the lesioned nigra and striatum. In summary, our data suggest that BMP7 has neuroprotective and/or neuroreparative effects against 6-OHDA lesioning of the nigrostriatal DA pathway in an animal model of Parkinson's disease (PD).
Harvey
B K
BK
National Institute on Drug Abuse, NIH, Neural Protection and Regeneration Section, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Mark
A
A
Chou
J
J
Chen
G J
GJ
Hoffer
B J
BJ
Wang
Y
Y
D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000627:therapeutic use*; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018765:Dopamine Uptake Inhibitors; D009414:Nerve Growth Factors; D008694:Methamphetamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D011188:Potassium; D004298:Dopamine