Single‐cell RNA sequencing integrated with bulk RNA sequencing analysis reveals the protective effects of lactate‐mediated lactylation of microglia‐related proteins on spinal cord injury

作者：Bin Zhang, Fudong Li, Yangyang Shi, Chenglong Ji, Qing‐Jie Kong, Kaiqiang Sun, Xiaofei Sun · 发表于：CNS Neuroscience & Therapeutics · 年份：2024 · DOI：10.1111/cns.70028 · 被引用次数：28 · 研究领域：Spinal Cord Injury Research、Neuroinflammation and Neurodegeneration Mechanisms、Neurogenesis and neuroplasticity mechanisms

Abstract Background and Objectives Spinal cord injury (SCI) results in significant neurological deficits, and microglia play the critical role in regulating the immune microenvironment and neurological recovery. Protein lactylation has been found to modulate the function of immune cells. Therefore, this study aimed to elucidate the effects of glycolysis‐derived lactate on microglial function and its potential neuroprotective mechanisms via lactylation after SCI. Methods Single‐cell RNA sequencing (scRNA‐seq) data were obtained from figshare to analyze cellular and molecular alterations within the spinal cord post‐SCI, further focusing on the expression of microglia‐related genes for cell sub‐clustering, trajectory analysis, and glycolysis function analysis. We also evaluated the expression of lactylation‐related genes in microglia between day 7 after SCI and sham group. Additionally, we established the mice SCI model and performed the bulk RNA sequencing in a time‐dependent manner. The expression of glycolysis‐ and lactylation‐related genes was evaluated, as well as the immune infiltration analysis based on the lactylation‐related genes. Then, we investigated the bio‐effects of lactate on the inflammation and polarization phenotype of microglia. Finally, adult male C57BL/6 mice were subjected to exercise first to increase lactate level, before SCI surgery, aiming to evaluate the protective effects of lactate‐mediated lactylation of microglia‐related proteins on SCI. Results s...