Intracranial infusion of monoamine-activated alpha 2-macroglobulin decreases dopamine concentrations within the rat caudate putamen.
Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit choline acetyltransferase in basal forebrain neurons as well as neurotrophin-dependent neuronal functions. The objective of this study was to determine whether monoamine-activated alpha 2M can affect the caudate putamen (CP) dopaminergic system in vivo. Male rats received intracranial infusions of methylamine-activated alpha 2M (0.6 nmole) and contralateral infusions of its vehicle, phosphate-buffered saline (PBS). Five days following infusion, the animals were killed, the CP dissected into three rostral-caudal segments, and assayed for dopamine (DA) using a high-performance liquid chromatography system. Within the two rostral CP segments (the approximate site of cannula placement), statistically significant (26%) reductions of DA concentrations were obtained on the alpha 2M-infused side of the CP with 90-100% of the animals showing decreases. At a more distal (caudal) site of the CP, DA concentrations showed only an insignificant (12%) reduction. No differences in DA concentrations between sides infused with bovine serum albumin versus PBS or from olfactory tubercle samples were obtained in these animals. These results demonstrate that monoamine-activated alpha 2M is capable of producing significant degeneration of the nigrostriatal dopaminergic system in vivo and suggest that this factor may play a role in age-related neurodegenerative disorders such as Parkinson's disease.
Hu
Y Q
YQ
Department of Microbiology and Immunology, Northeastern Ohio Universities College of Medicine, Rootstown 44272.
Dluzen
D E
DE
Koo
P H
PH
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007260:Infusion Pumps; D008297:Male; D009410:Nerve Degeneration; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000511:alpha-Macroglobulins / Q000494:pharmacology* / Q000502:physiology / Q000633:toxicity
D000511:alpha-Macroglobulins; D004298:Dopamine