Manganese exposure inhibits the clearance of extracellular GABA and influences taurine homeostasis in the striatum of developing rats.
Manganese exposure inhibits the clearance of extracellular GABA and influences taurine homeostasis in the striatum of developing rats.
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DOI：
10.1016/j.neuro.2010.09.002
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发表时间：
2010-12
期刊：
影响因子：
3.4
通讯作者：
Erikson KM
中科院分区：
文献类型：
--
作者：
Fordahl SC;Anderson JG;Cooney PT;Weaver TL;Colyer CL;Erikson KM
锰（Mn）在大脑中的积累已被证明会改变基底神经节的神经化学。锰诱导的多巴胺生物学改变是相当好理解的，但最近出现了更多的证据，表明γ-氨基丁酸（GABA）在这种功能障碍中的作用。本研究的目的是确定先前观察到的Mn诱导的细胞外GABA（GABAEC）增加是否是由于GABA转运蛋白（GAT）功能改变，以及Mn是否干扰其他氨基酸神经递质，即牛磺酸和甘氨酸（已知的GABA调节剂）。细胞外GABA，牛磺酸和甘氨酸浓度收集从纹状体的控制（CN）或锰暴露的Sprague-Dawley大鼠使用体内微透析，和GAT抑制剂哌啶甲酸（NA）被用来探测GAT功能。组织和细胞外锰水平显着增加，和铁：锰的比例降低了36倍，由于锰暴露在细胞外空间。NA导致氯化萘的GABAEC增加2倍，锰则减弱了这种反应。牛磺酸对GABA的反应与之相反，在去除氯化萘中的NA后，观察到牛磺酸增加了10倍。锰减弱了这种反应，并在整个收集过程中几乎消除了细胞外牛磺酸。纹状体牛磺酸转运体（Slc 6a 6）的mRNA水平显着增加与锰暴露，锰显着增加3 H-牛磺酸摄取后3分钟暴露在原代大鼠星形胶质细胞。这些数据表明，锰通过抑制GAT的功能增加GABAEC，并且扰乱的牛磺酸稳态可能通过危害牛磺酸在脑中的神经调节和神经调节功能来影响神经功能。
Manganese (Mn) accumulation in the brain has been shown to alter the neurochemistry of the basal ganglia. Mn-induced alterations in dopamine biology are fairly well understood, but recently more evidence has emerged characterizing the role of γ-aminobutyric acid (GABA) in this dysfunction. The purpose of this study was to determine if the previously observed Mn-induced increase in extracellular GABA (GABAEC) was due to altered GABA transporter (GAT) function, and whether Mn perturbs other amino acid neurotransmitters, namely taurine and glycine (known modulators of GABA). Extracellular GABA, taurine, and glycine concentrations were collected from the striatum of control (CN) or Mn-exposed Sprague-Dawley rats using in vivo microdialysis, and the GAT inhibitor nipecotic acid (NA) was used to probe GAT function. Tissue and extracellular Mn levels were significantly increased, and the Fe:Mn ratio was decreased 36-fold in the extracellular space due to Mn exposure. NA led to a 2-fold increase in GABAEC of CNs, a response that was attenuated by Mn. Taurine responded inversely to GABA, and a novel 10-fold increase in taurine was observed after the removal of NA in CNs. Mn blunted this response and nearly abolished extracellular taurine throughout collection. Striatal taurine transporter (Slc6a6) mRNA levels were significantly increased with Mn exposure, and Mn significantly increased 3H-Taurine uptake after 3-minute exposure in primary rat astrocytes. These data suggest that Mn increases GABAEC by inhibiting the function of GAT, and that perturbed taurine homeostasis potentially impacts neural function by jeopardizing the osmoregulatory and neuromodulatory functions of taurine in the brain.
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影响因子：
3.4
作者：
Cowan DM;Zheng W;Zou Y;Shi X;Chen J;Rosenthal FS;Fan Q
通讯作者：
Fan Q
影响因子：
3.8
作者：
Garcia, Stephanie J.;Gellein, Kristin;Aschner, Michael
通讯作者：
Aschner, Michael
影响因子：
3.4
作者：
del Olmo, N;Suárez, LM;Solís, JM
通讯作者：
Solís, JM
DOI：
10.1196/annals.1306.009
发表时间：
2004-01-01
期刊：
REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS
影响因子：
--
作者：
Dobson, AW;Erikson, KM;Aschner, M
通讯作者：
Aschner, M
影响因子：
3.8
作者：
Anderson, Joel G.;Cooney, Paula T.;Erikson, Keith M.
通讯作者：
Erikson, Keith M.