Cargando…
L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain
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...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409556/ https://www.ncbi.nlm.nih.gov/pubmed/22888467 http://dx.doi.org/10.1155/2012/321406 |
_version_ | 1782239609514622976 |
---|---|
author | 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. |
author_facet | 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. |
author_sort | Inyushin, M. Y. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3409556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-34095562012-08-10 L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain 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. Parkinsons Dis Research Article 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. Hindawi Publishing Corporation 2012 2012-07-24 /pmc/articles/PMC3409556/ /pubmed/22888467 http://dx.doi.org/10.1155/2012/321406 Text en Copyright © 2012 M. Y. Inyushin et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article 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. L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain |
title | L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain |
title_full | L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain |
title_fullStr | L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain |
title_full_unstemmed | L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain |
title_short | L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain |
title_sort | l-dopa uptake in astrocytic endfeet enwrapping blood vessels in rat brain |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409556/ https://www.ncbi.nlm.nih.gov/pubmed/22888467 http://dx.doi.org/10.1155/2012/321406 |
work_keys_str_mv | AT inyushinmy ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT huertasa ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT kucheryavykhyv ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT kucheryavykhly ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT tsydzikv ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT sanabriap ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT eatonmj ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT skatchkovsn ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT rojaslv ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain AT wessingerwd ldopauptakeinastrocyticendfeetenwrappingbloodvesselsinratbrain |