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Updated: May 10, 2025
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
Differential changes in the microglial transcriptome between neonatal and adult mice after spinal cord injury
Qi Jiang1,2, Shiyuan Xue1,2, Xiaojing Pan3
1Department of Sports Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
Abstract:
Spinal cord injury (SCI) remains a significant therapeutic challenge, lacking effective treatment options. Related studies have found that neonatal microglia are more effective than adult microglia in promoting the recovery of SCI, but the reason why neonatal, not adult, microglia are more conducive to SCI recovery is not clear, the differences of gene expression and pathways between them are still worth exploring. Therefore, we examined changes in the microglial transcriptome after SCI in neonatal and adult mice. We identified hub genes or pathways that exhibited significant differential expression between the two groups. Four Gene sets were established for further analysis, named Gene set 1, Gene set 2, Gene set 3, Gene set 4, respectively. GO analysis revealed enrichment in categories critical for injury repair, including DNA metabolism, replication, recombination, meiotic cell cycle progression, regulation of cell-cell adhesion, megakaryocyte and endothelial development, modulation of the neuroinflammatory response, endocytosis, and regulation of cytokine production and cell migration. KEGG analysis revealed enrichment in pathways critical for various cellular processes, including the p53, TNF, PI3K-AKT, PPAR and B cell receptor signaling pathway, axon guidance, cytokine-cytokine receptor interaction. PPI and TF-hub gene-microRNA networks were constructed to elucidate the underlying gene regulatory mechanisms. Additionally, drug prediction was performed to identify potential therapeutic candidates. Finally, 11 hub genes (Chek1, RRM2, Lyve1, Mboat1, Clec4a3, Ccnd1, Cdk6, Zeb1, Igf1, Pparg, and Cd163) were selected from four Gene sets for further validation using qRT-PCR. We identified candidate genes and pathways involved in microglial transcriptome heterogeneity after SCI in neonatal and adult mice. These findings provide valuable insights into potential therapeutic targets for neonatal microglia in the treatment of SCI.
Insights
Neonatal microglia promote spinal cord injury (SCI) recovery more effectively than adult microglia. This study identifies key gene expression differences and pathways, revealing potential therapeutic targets for SCI treatment.
Area of Science:
- Neuroscience
- Immunology
- Genomics
Background:
- Spinal cord injury (SCI) presents a major therapeutic challenge with limited effective treatments.
- Neonatal microglia show greater efficacy in promoting SCI recovery compared to adult microglia, but the underlying reasons remain unclear.
Purpose of the Study:
- To investigate the differences in microglial gene expression and pathways between neonatal and adult mice following SCI.
- To identify key genes and pathways that contribute to the superior recovery observed with neonatal microglia.
Main Methods:
- Comparative transcriptomic analysis of microglia from neonatal and adult mice post-SCI.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
- Construction of protein-protein interaction (PPI) and transcription factor-hub gene-microRNA networks.
- Drug prediction and validation of 11 selected hub genes using qRT-PCR.
Main Results:
- Significant differential gene expression and pathway enrichment were identified between neonatal and adult microglia.
- Key enriched categories include DNA metabolism, cell cycle regulation, cell adhesion, neuroinflammation modulation, and cytokine signaling.
- Eleven hub genes (e.g., Chek1, RRM2, Igf1, Pparg) were identified as potential regulators of microglial function post-SCI.
Conclusions:
- Microglial heterogeneity significantly impacts SCI recovery, with distinct transcriptomic profiles in neonatal versus adult mice.
- The identified genes and pathways offer novel therapeutic targets for enhancing SCI treatment using neonatal microglia-derived strategies.
