Xu Jinying, Zheng Yangyang, Lv Shuang, Kang Juanjuan, Yu Yifei, Hou Kun, Li Yulin, Chi Guangfan
The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, PR China.
Neuroscience. 2020 Aug 21;442:54-68. doi: 10.1016/j.neuroscience.2020.06.041. Epub 2020 Jul 4.
During cerebral ischemia, brain lactate concentration increases, and astrogliosis is triggered. Herein, we investigated lactate's role in astrogliosis and explored the functions of lactate-activated astrocytes in vitro. In rat models of cerebral ischemia, we observed increased glial fibrillary acidic protein (GFAP) expression, reflecting astrogliosis, and increased lactate levels in the ischemic brain region. Lactate upregulated GFAP and SRY-box transcription factor 9 (SOX9) expression and activated Akt and signal transducer and activator of transcription 3 (STAT3) signaling pathways in astrocytes cultured under oxygen-glucose deprivation (OGD); these effects were abrogated upon monocarboxylate transporter 1 (MCT1) knockdown. RNA-Seq analysis revealed 221 differentially expressed genes (DEGs) between lactate-treated and untreated astrocytes. Genes upregulated by lactate treatment included those regulating astrogliosis and axon guidance. Consistently, lactate-treated astrocytes induced neuronal outgrowth upon coculture. Our results suggest that lactate promotes reactive astrogliosis and confers axon guidance potential to astrocytes under OGD.
在脑缺血期间，脑乳酸浓度升高，并引发星形胶质细胞增生。在此，我们研究了乳酸在星形胶质细胞增生中的作用，并在体外探索了乳酸激活的星形胶质细胞的功能。在脑缺血大鼠模型中，我们观察到反映星形胶质细胞增生的胶质纤维酸性蛋白（GFAP）表达增加，以及缺血脑区乳酸水平升高。乳酸上调了在氧-葡萄糖剥夺（OGD）条件下培养的星形胶质细胞中GFAP和SRY盒转录因子9（SOX9）的表达，并激活了Akt和信号转导及转录激活因子3（STAT3）信号通路；在单羧酸转运体1（MCT1）敲低后，这些效应被消除。RNA测序分析揭示了乳酸处理组和未处理组星形胶质细胞之间有221个差异表达基因（DEG）。乳酸处理上调的基因包括那些调节星形胶质细胞增生和轴突导向的基因。一致地，乳酸处理的星形胶质细胞在共培养时诱导神经元生长。我们的结果表明，乳酸促进反应性星形胶质细胞增生，并赋予OGD条件下的星形胶质细胞轴突导向潜能。
