Glial Chloride Homeostasis Under Transient Ischemic Stress.
Glial Chloride Homeostasis Under Transient Ischemic Stress.
复制标题
DOI：
10.3389/fncel.2021.735300
复制
发表时间：
2021
影响因子：
5.3
通讯作者：
Fahlke C
中科院分区：
文献类型：
--
作者：
Engels M;Kalia M;Rahmati S;Petersilie L;Kovermann P;van Putten MJAM;Rose CR;Meijer HGE;Gensch T;Fahlke C
高的水渗透性使胶质细胞的体积随着内外渗透压的变化而迅速调整，病理改变的细胞内氯离子浓度([Cl-]INT)和胶质细胞肿胀通常被认为是脑缺血、感染或创伤性脑损伤的早期事件。神经胶质[Cl-]int的实验数据在大多数脑区都是缺乏的，无论是在正常情况下还是在病理条件下。在室温下，我们用氯离子敏感染料MQAE，用荧光寿命成像显微镜测量了急性脑片中海马区和新皮质星形胶质细胞以及海马区放射状胶质样细胞中的[Cl-]int。我们观察到基线[Cl-]int的异质性，从新皮质星形胶质细胞的14.0±2.0 mm到齿状回星形胶质细胞的28.4±3.0 mm不等。在不同脑区，Na+-K+-2Cl-转运体(NKCC1)的氯离子蓄积和K+-Cl-转运体(KCC1和KCC3)或兴奋性氨基酸转运体(EAAT)阴离子通道对氯离子的外向转运(外流)控制着不同程度的[Cl-]int。在海马星形胶质细胞中，阻断NKCC1可降低[Cl-]INT，而抑制KCC或EAAT阴离子通道作用不明显。相反，新皮质星形胶质细胞或Rgl[Cl-]int对氯离子的外向转运阻断非常敏感，但对NKCC1抑制作用不敏感。数学模型表明，NKCC1和KCC转运体数量较多可以解释新皮质比海马星形胶质细胞[Cl-]Int低的原因。模拟脑缺血10min的能量耗竭不会导致任何受试神经胶质细胞类型的[Cl-]int发生明显变化。然而，在阻断选定的阴离子转运体后，[Cl-]int在缺血条件下发生了变化。我们得出结论，在瞬时能量剥夺条件下，受刺激的氯离子积累和氯离子外流相互补偿，防止胶质细胞肿胀。
High water permeabilities permit rapid adjustments of glial volume upon changes in external and internal osmolarity, and pathologically altered intracellular chloride concentrations ([Cl–]int) and glial cell swelling are often assumed to represent early events in ischemia, infections, or traumatic brain injury. Experimental data for glial [Cl–]int are lacking for most brain regions, under normal as well as under pathological conditions. We measured [Cl–]int in hippocampal and neocortical astrocytes and in hippocampal radial glia-like (RGL) cells in acute murine brain slices using fluorescence lifetime imaging microscopy with the chloride-sensitive dye MQAE at room temperature. We observed substantial heterogeneity in baseline [Cl–]int, ranging from 14.0 ± 2.0 mM in neocortical astrocytes to 28.4 ± 3.0 mM in dentate gyrus astrocytes. Chloride accumulation by the Na+-K+-2Cl– cotransporter (NKCC1) and chloride outward transport (efflux) through K+-Cl– cotransporters (KCC1 and KCC3) or excitatory amino acid transporter (EAAT) anion channels control [Cl–]int to variable extent in distinct brain regions. In hippocampal astrocytes, blocking NKCC1 decreased [Cl–]int, whereas KCC or EAAT anion channel inhibition had little effect. In contrast, neocortical astrocytic or RGL [Cl–]int was very sensitive to block of chloride outward transport, but not to NKCC1 inhibition. Mathematical modeling demonstrated that higher numbers of NKCC1 and KCC transporters can account for lower [Cl–]int in neocortical than in hippocampal astrocytes. Energy depletion mimicking ischemia for up to 10 min did not result in pronounced changes in [Cl–]int in any of the tested glial cell types. However, [Cl–]int changes occurred under ischemic conditions after blocking selected anion transporters. We conclude that stimulated chloride accumulation and chloride efflux compensate for each other and prevent glial swelling under transient energy deprivation.
登录
查看更多内容
影响因子：
--
作者：
Berg DA;Bond AM;Ming GL;Song H
通讯作者：
Song H
影响因子：
4.2
作者：
Gerkau, Niklas J.;Rakers, Cordula;Rose, Christine R.
通讯作者：
Rose, Christine R.
KCC3在维持周围神经纤维的细胞体积中的作用。
影响因子：
4.2
作者：
Flores B;Schornak CC;Delpire E
通讯作者：
Delpire E
影响因子：
6.2
作者：
Brunne, Bianka;Zhao, Shanting;Derouiche, Amin;Herz, Joachim;May, Petra;Frotscher, Michael;Bock, Hans H.
通讯作者：
Bock, Hans H.
影响因子：
4.2
作者：
Benesova, Jana;Hock, Miroslav;Chvatal, Alexander
通讯作者：
Chvatal, Alexander