Heterogeneity of astrocytes: Electrophysiological properties of juxtavascular astrocytes before and after brain injury
Heterogeneity of astrocytes: Electrophysiological properties of juxtavascular astrocytes before and after brain injury
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DOI：
10.1002/glia.23900
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发表时间：
2020-08-18
期刊：
影响因子：
6.2
通讯作者：
Kunz, Lars
中科院分区：
文献类型：
--
作者：
Goetz, Stefanie;Bribian, Ana;Kunz, Lars
尽管星形胶质细胞在脑损伤后具有重要意义，但人们越来越认识到星形胶质细胞的异质性，但对其躯体直接邻近血管的血管旁星形胶质细胞知之甚少。由于血管旁星形胶质细胞起源于共同祖细胞，即具有克隆起源，因此它们可能与其他非血管旁星形胶质细胞存在本质差异。为了探讨这一点，我们检查了这些星形胶质细胞群的电生理特性和潜在的离子通道。采用GFP标记星形胶质细胞的BAC Aldh1l1-eGFP转基因小鼠脑切片，通过全细胞膜片钳记录和免疫组织化学染色比较体感觉皮层血管旁和非血管旁星形胶质细胞的差异。损伤前，血管旁和非血管旁星形胶质细胞表现出相似的电生理特性，主要表现为被动电导和典型的负静息膜电位。K（+）通道的免疫组织化学分析显示，所有星形胶质细胞都是K(ir)4.1(+)，但K(v)4.3有一个有趣的差异。K(v)4.3在同胞星形胶质细胞（非血管旁细胞、血管旁细胞和脑膜旁细胞）中的表达依赖于它们的个体起源，位于皮质上层的血管旁星形胶质细胞中表达水平最低。在创伤性脑损伤（TBI）后，我们发现星形胶质细胞的电生理类型发生了深刻的变化，其非被动性质占主导地位，这种模式在血管旁星形胶质细胞中显著增强。这伴随着增殖星形胶质细胞中K(ir)4.1的明显下调，与非血管旁星形胶质细胞相比，血管旁星形胶质细胞中的K(ir)4.1明显下调。综上所述，创伤性脑损伤在血管旁和非血管旁星形胶质细胞之间引起了电生理特性的深刻差异，这可能与血管旁星形胶质细胞增殖优势有关。
Astrocyte heterogeneity is increasingly recognized, but still little is known about juxtavascular astrocytes with their somata directly adjacent to blood vessels, despite their importance after brain injury. As juxtavascular astrocytes originate from common progenitor cells, that is, have a clonal origin, they may intrinsically differ from other, non-juxtavascular astrocytes. To explore this, we examined the electrophysiological properties of these groups of astrocytes and the underlying ion channels. Using brain slices of BAC Aldh1l1-eGFP transgenic mice with astrocytes labeled by GFP expression, we compared juxtavascular and non-juxtavascular astrocytes in the somatosensory cortex by means of whole-cell patch-clamp recordings and immunohistochemical staining. Prior to injury, juxta- and non-juxtavascular astrocytes exhibit comparable electrophysiological properties with characteristic mostly passive conductance and a typical negative resting membrane potential. Immunohistochemical analysis of K(+)channels showed that all astrocytes were K(ir)4.1(+), but revealed an intriguing difference for K(v)4.3. The expression of K(v)4.3 in sibling astrocytes (non-juxtavascular, juxtavascular and pial) was dependent on their ontogenetic origin with lowest levels in juxtavascular astrocytes located in upper cortical layers. After traumatic brain injury (TBI), we found profound changes in the electrophysiological type of astrocytes with a predominance of non-passive properties and this pattern was significantly enriched in juxtavascular astrocytes. This was accompanied by pronounced down-regulation of K(ir)4.1 in proliferating astrocytes, which was significantly more in juxtavascular compared to non-juxtavascular astrocytes. Taken together, TBI induces profound differences in electrophysiological properties between juxtavascular and non-juxtavascular astrocytes that might be related to the preponderance of juxtavascular astrocyte proliferation.