Striatal astrocytes act as a reservoir for L-DOPA.

L-DOPA is therapeutically efficacious in patients with Parkinson's disease (PD), although dopamine (DA) neurons are severely degenerated. Since cortical astrocytes express neutral amino acid transporter (LAT) and DA transporter (DAT), the uptake and metabolism of L-DOPA and DA in striatal astro...

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Autores principales:	Masato Asanuma, Ikuko Miyazaki, Shinki Murakami, Francisco J Diaz-Corrales, Norio Ogawa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d3d1a899d08d4c9a853ca5954dbae6ca
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spelling	oai:doaj.org-article:d3d1a899d08d4c9a853ca5954dbae6ca2021-11-25T06:01:53ZStriatal astrocytes act as a reservoir for L-DOPA.1932-620310.1371/journal.pone.0106362https://doaj.org/article/d3d1a899d08d4c9a853ca5954dbae6ca2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25188235/?tool=EBIhttps://doaj.org/toc/1932-6203L-DOPA is therapeutically efficacious in patients with Parkinson's disease (PD), although dopamine (DA) neurons are severely degenerated. Since cortical astrocytes express neutral amino acid transporter (LAT) and DA transporter (DAT), the uptake and metabolism of L-DOPA and DA in striatal astrocytes may influence their availability in the dopaminergic system of PD. To assess possible L-DOPA- and DA-uptake and metabolic properties of striatal astrocytes, we examined the expression of L-DOPA, DA and DAT in striatal astrocytes of hemi-parkinsonian model rats after repeated L-DOPA administration, and measured the contents of L-DOPA, DA and their metabolite in primary cultured striatal astrocytes after L-DOPA/DA treatment. Repeated injections of L-DOPA induced apparent L-DOPA- and DA-immunoreactivities and marked expression of DAT in reactive astrocytes on the lesioned side of the striatum in hemi-parkinsonian rats. Exposure to DA for 4h significantly increased the levels of DA and its metabolite DOPAC in cultured striatal astrocytes. L-DOPA was also markedly increased in cultured striatal astrocytes after 4-h L-DOPA exposure, but DA was not detected 4 or 8h after L-DOPA treatment, despite the expression of aromatic amino acid decarboxylase in astrocytes. Furthermore, the intracellular level of L-DOPA in cultured striatal astrocytes decreased rapidly after removal of extracellular L-DOPA. The results suggest that DA uptaken into striatal astrocytes is rapidly metabolized and that striatal astrocytes act as a reservoir of L-DOPA that govern the uptake or release of L-DOPA depending on extracellular L-DOPA concentration, but are less capable of converting L-DOPA to DA.Masato AsanumaIkuko MiyazakiShinki MurakamiFrancisco J Diaz-CorralesNorio OgawaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e106362 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masato Asanuma Ikuko Miyazaki Shinki Murakami Francisco J Diaz-Corrales Norio Ogawa Striatal astrocytes act as a reservoir for L-DOPA.
description	L-DOPA is therapeutically efficacious in patients with Parkinson's disease (PD), although dopamine (DA) neurons are severely degenerated. Since cortical astrocytes express neutral amino acid transporter (LAT) and DA transporter (DAT), the uptake and metabolism of L-DOPA and DA in striatal astrocytes may influence their availability in the dopaminergic system of PD. To assess possible L-DOPA- and DA-uptake and metabolic properties of striatal astrocytes, we examined the expression of L-DOPA, DA and DAT in striatal astrocytes of hemi-parkinsonian model rats after repeated L-DOPA administration, and measured the contents of L-DOPA, DA and their metabolite in primary cultured striatal astrocytes after L-DOPA/DA treatment. Repeated injections of L-DOPA induced apparent L-DOPA- and DA-immunoreactivities and marked expression of DAT in reactive astrocytes on the lesioned side of the striatum in hemi-parkinsonian rats. Exposure to DA for 4h significantly increased the levels of DA and its metabolite DOPAC in cultured striatal astrocytes. L-DOPA was also markedly increased in cultured striatal astrocytes after 4-h L-DOPA exposure, but DA was not detected 4 or 8h after L-DOPA treatment, despite the expression of aromatic amino acid decarboxylase in astrocytes. Furthermore, the intracellular level of L-DOPA in cultured striatal astrocytes decreased rapidly after removal of extracellular L-DOPA. The results suggest that DA uptaken into striatal astrocytes is rapidly metabolized and that striatal astrocytes act as a reservoir of L-DOPA that govern the uptake or release of L-DOPA depending on extracellular L-DOPA concentration, but are less capable of converting L-DOPA to DA.
format	article
author	Masato Asanuma Ikuko Miyazaki Shinki Murakami Francisco J Diaz-Corrales Norio Ogawa
author_facet	Masato Asanuma Ikuko Miyazaki Shinki Murakami Francisco J Diaz-Corrales Norio Ogawa
author_sort	Masato Asanuma
title	Striatal astrocytes act as a reservoir for L-DOPA.
title_short	Striatal astrocytes act as a reservoir for L-DOPA.
title_full	Striatal astrocytes act as a reservoir for L-DOPA.
title_fullStr	Striatal astrocytes act as a reservoir for L-DOPA.
title_full_unstemmed	Striatal astrocytes act as a reservoir for L-DOPA.
title_sort	striatal astrocytes act as a reservoir for l-dopa.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d3d1a899d08d4c9a853ca5954dbae6ca
work_keys_str_mv	AT masatoasanuma striatalastrocytesactasareservoirforldopa AT ikukomiyazaki striatalastrocytesactasareservoirforldopa AT shinkimurakami striatalastrocytesactasareservoirforldopa AT franciscojdiazcorrales striatalastrocytesactasareservoirforldopa AT norioogawa striatalastrocytesactasareservoirforldopa
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Striatal astrocytes act as a reservoir for L-DOPA.

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