Persistent Overexposure to N-Methyl-D-Aspartate (NMDA) Calcium-Dependently Downregulates Glutamine Synthetase, Aquaporin 4, and Kir4.1 Channel in Mouse Cortical Astrocytes.

Persistent Overexposure to N-Methyl-D-Aspartate (NMDA) Calcium-Dependently Downregulates Glutamine Synthetase, Aquaporin 4, and Kir4.1 Channel in Mouse Cortical Astrocytes.
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DOI:
10.1007/s12640-018-9958-3
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发表时间:
2019-01
影响因子:
3.7
通讯作者:
Albrecht J
Albrecht J
中科院分区:
医学3区
文献类型:
--
作者:
Skowrońska K;Obara-Michlewska M;Czarnecka A;Dąbrowska K;Zielińska M;Albrecht J

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星形胶质细胞表达N-甲基-d-天冬氨酸受体(NMDAR),但其在这些细胞中的功能尚不清楚。本研究表明,小鼠星形胶质细胞持续暴露于NMDA(8-72小时)会降低星形胶质细胞功能蛋白谷氨酰胺合成酶(GS)和水通道蛋白AQP4的表达,并降低GS的活性。与大鼠星形胶质细胞相似(Obara-Michlewska等人)。Neurochem Int 88:20-25,),小鼠星形胶质细胞暴露于NMDA也降低了内向整流钾通道Kir4.1的表达。NMDA未能在无钙孵育的细胞中以及在NMDAR的GluN1亚单位被GluN1 siRNA沉默的细胞中产生这种效应。在体外观察到的GS、AQP4和Kir4.1的下调可能反映了NMDAR介导的星形胶质细胞功能的改变,在与谷氨酸(Glu)释放增加和兴奋性组织损伤相关的中枢神经系统病理中。
Astrocytes express N-methyl-d-aspartate (NMDA) receptor (NMDAR) but its functions in these cells are not well defined. This study shows that the sustained exposure (8–72 h) of mouse astrocytes to NMDA decreases the expression of the functional astroglia-specific proteins, glutamine synthetase (GS), and the water channel protein aquaporin-4 (AQP4) and also reduces GS activity. Similar to rat astrocytes (Obara-Michlewska et al. Neurochem Int 88:20–25,), the exposure of mouse astrocytes to NMDA also decreased the expression of the inward rectifying potassium channel Kir4.1. NMDA failed to elicit the effects in those cells incubated in the absence of Ca2+ and in those in which the GluN1 subunit of the NMDAR was silenced with GluN1 siRNA. The downregulation of GS, AQP4, and Kir4.1 observed in vitro may reflect NMDAR-mediated alterations of astrocytic functions noted in central nervous system pathologies associated with increased glutamate (Glu) release and excitotoxic tissue damage.
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