Striatal astrocytes act as a reservoir for L-DOPA.
Striatal astrocytes act as a reservoir for L-DOPA.
复制标题
纹状体星形胶质细胞充当左旋多巴的储存库。
DOI：
10.1371/journal.pone.0106362
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ogawa N
中科院分区：
文献类型：
--
作者：
Asanuma M;Miyazaki I;Murakami S;Diaz-Corrales FJ;Ogawa N
尽管多巴胺(DA)神经元严重变性，L多巴对帕金森病(PD)患者仍有疗效。由于皮质星形胶质细胞表达中性氨基酸转运体(LAT)和多巴胺转运体(DAT)，纹状体星形胶质细胞对L-多巴和多巴胺的摄取和代谢可能影响它们在帕金森病多巴胺能系统中的利用率。为了探讨纹状体星形胶质细胞对L多巴和多巴胺的摄取和代谢特性，我们检测了反复给予L多巴的偏侧帕金森模型大鼠纹状体星形胶质细胞中L多巴、多巴胺和多巴胺的表达，以及L多巴和多巴胺处理后原代培养的纹状体星形胶质细胞L多巴、多巴胺及其代谢物的含量。反复注射L多巴可诱导帕金森病大鼠损毁侧纹状体反应性星形胶质细胞出现明显的L多巴和多巴胺免疫反应及DAT的显著表达。DA作用4h可显著增加培养的纹状体星形胶质细胞DA及其代谢产物DOPAC的水平。在培养的纹状体星形胶质细胞中，L-多巴作用4h后也明显增加，但在L-多巴作用4h和8h后，尽管星形胶质细胞表达了芳香氨基酸脱羧酶，但仍未检测到多巴胺。此外，去除细胞外的L多巴后，培养的纹状体星形胶质细胞内L多巴水平迅速下降。结果提示，多巴胺被纹状体星形胶质细胞迅速代谢，并且纹状体星形胶质细胞作为L-多巴的储存库，其摄取或释放L-多巴的能力取决于细胞外L-多巴的浓度，但将L-多巴转化为DA的能力较弱。
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.
登录
查看更多内容
影响因子：
2.9
作者：
Inazu, M;Takeda, H;Matsumiya, T
通讯作者：
Matsumiya, T
影响因子：
11.2
作者：
Rylander, Daniella;Parent, Martin;Cenci, M. Angela
通讯作者：
Cenci, M. Angela
DOI：
10.1155/2012/321406
发表时间：
2012
期刊：
Parkinson's disease
影响因子：
--
作者：
Inyushin MY;Huertas A;Kucheryavykh YV;Kucheryavykh LY;Tsydzik V;Sanabria P;Eaton MJ;Skatchkov SN;Rojas LV;Wessinger WD
通讯作者：
Wessinger WD
DOI：
10.1016/j.nurt.2010.07.006
发表时间：
2010-10
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Kimelberg HK;Nedergaard M
通讯作者：
Nedergaard M
影响因子：
6.2
作者：
Miyazaki, Ikuko;Asanuma, Masato;Kita, Taizo
通讯作者：
Kita, Taizo