Division of Neurobiology, Department of Biology II, Ludwig-Maximilians-Universitaet (LMU) Munich, Martinsried, Germany.
Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universitaet (LMU) Munich, Martinsried, Germany.
Glia. 2021 Feb;69(2):346-361. doi: 10.1002/glia.23900. Epub 2020 Aug 18.
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 4.1 , but revealed an intriguing difference for K 4.3. The expression of K 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 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.
星形胶质细胞的异质性正日益受到重视，但对于紧邻血管的血管周星形胶质细胞（其胞体直接与血管相邻），尽管它们在脑损伤后很重要，但仍知之甚少。由于血管周星形胶质细胞起源于共同的祖细胞，即具有克隆起源，因此它们可能在内在上与其他非血管周星形胶质细胞不同。为了探索这一点，我们研究了这些星形胶质细胞群的电生理特性及其潜在的离子通道。我们使用 BAC Aldh1l1-eGFP 转基因小鼠的脑切片，该小鼠的星形胶质细胞通过 GFP 表达进行标记，通过全细胞膜片钳记录和免疫组织化学染色，比较了体感皮层中的血管周和非血管周星形胶质细胞。在损伤之前，血管周和非血管周星形胶质细胞表现出相似的电生理特性，具有典型的主要被动电导和典型的负静息膜电位。对 K 通道的免疫组织化学分析表明，所有星形胶质细胞均表达 K 4.1 ，但 K 4.3 的表达却存在有趣的差异。K 4.3 在同胞星形胶质细胞（非血管周、血管周和软脑膜）中的表达依赖于它们的起源，在上皮层中的血管周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变化，非被动特性占主导地位，这种模式在血管周星形胶质细胞中明显更为丰富。这伴随着增殖星形胶质细胞中 K 4.1 的明显下调，与非血管周星形胶质细胞相比，血管周星形胶质细胞中的下调更为明显。总之，TBI 在血管周和非血管周星形胶质细胞之间诱导了电生理特性的深刻差异，这可能与血管周星形胶质细胞增殖的优势有关。
