L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain. (24th July 2012)

• Record Type: Journal Article
• Authors: Inyushin, M. Y.; Huertas, A.; Kucheryavykh, Y. V.; Kucheryavykh, L. Y.; Tsydzik, V.; Sanabria, P.; Eaton, M. J.; Skatchkov, S. N.; Rojas, L. V.; Wessinger, W. D.
• Other Names: Reichmann Heinz Academic Editor.
• Is Part Of: Parkinson's disease. Volume 2012(2012)
• Publication Date: 2012-07-24
• Subjects: Parkinson's disease -- Periodicals; Parkinson's disease -- Treatment -- Periodicals; 616.833005
• DOI: 10.1155/2012/321406
• Languages: English
• ISSNs: 2090-8083

Abstract

Abstract : Astrocyte endfeet surround brain blood vessels and can play a role in the delivery of therapeutic drugs for Parkinson's disease. However, there is no previous evidence of the presence of LAT transporter for L -DOPA in brain astrocytes except in culture. Using systemic L -DOPA administration and a combination of patch clamp, histochemistry and confocal microscopy we found that L -DOPA is accumulated mainly in astrocyte cell bodies, astrocytic endfeet surrounding blood vessels, and pericytes. In brain slices: (1) astrocytes were exposed to ASP +, a fluorescent monoamine analog of MPP + ; (2) ASP + taken up by astrocytes was colocalized with L -DOPA fluorescence in (3) glial somata and in the endfeet attached to blood vessels; (4) these astrocytes have an electrogenic transporter current elicited by ASP +, but intriguingly not by L -DOPA, suggesting a different pathway for monoamines and L -DOPA via astrocytic membrane. (5) The pattern of monoamine oxidase (MAO type B) allocation in pericytes and astrocytic endfeet was similar to that of L -DOPA accumulation. We conclude that astrocytes control L -DOPA uptake and metabolism and, therefore, may play a key role in regulating brain dopamine level during dopamine-associated diseases. These data also suggest that different transporter mechanisms may exist for monoamines and L -DOPA.