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，脑乳酸浓度增加，并引发星形胶质细胞增多症。在这里，我们调查了乳酸在星形胶质细胞增生中的作用，并探讨了乳酸激活的星形胶质细胞的体外功能。在脑缺血的大鼠模型中，我们观察到神经胶质纤维酸性蛋白（GFAP）的表达增加，反映了星形胶质细胞增生，而缺血性脑区域的乳酸水平也升高。在氧-葡萄糖剥夺（OGD）下培养的星形胶质细胞中，乳酸上调了GFAP和SRY-box转录因子9（SOX9）的表达，并激活了Akt和信号转导和转录激活子（STAT3）信号通路；这些作用在单羧酸盐转运蛋白1（MCT1）敲低后被废止。RNA-Seq分析揭示了在乳酸处理和未处理的星形胶质细胞之间存在221个差异表达的基因（DEG）。乳酸处理上调的基因包括调节星形胶质细胞增多症和轴突引导的基因。一致地，经乳酸盐处理的星形胶质细胞在共培养时诱导神经元生长。