BDNF-GABA signaling in astrocytes: enhancing neural repair after SCI through MSC therapies.

Study design: An integrated bioinformatics data study.

Objective: This study, through bioinformatics analysis, aims to map the landscape of astrocytes, explore key signaling pathways, and uncover molecular mechanisms that support SCI recovery facilitated by MSCs and iPSCs.

Setting: Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University.

Methods: We performed a bioinformatics analysis of single-cell transcriptomes (scRNA-seq), spatial transcriptomics, and bulk RNA-seq data sourced from Gene Expression Omnibus (GEO) datasets. The data processing involved R packages like "Seurat," "DESeq2," and "WGCNA." For pathway enrichment, we used Gene Set Enrichment Analysis (GSEA) and the Enrichr web server.

Results: Single-cell and spatial transcriptomic analysis revealed notable changes in the astrocyte landscape after SCI, highlighting a significant disruption in astrocyte populations within the injured region. Findings suggest that BDNF regulation of GABA neurotransmission and GABA receptor signaling in astrocytes plays a key role in promoting neuronal regeneration. Additionally, hUC-MSCs were found to enhance neural repair by activating BDNF-regulated GABA signaling of astrocytes. A promising alternative involves iPS-derived MSCs, which have shown potential to boost neural regeneration through BDNF, GABA, and GABA receptor signaling pathways of astrocytes.

Conclusions: In summary, SCI disrupts astrocyte populations, impacting their ability to support neural repair. BDNF-regulated GABA signaling in astrocytes is essential for neuron regeneration. Both hUC-MSCs and iPS-derived MSCs show promise in enhancing neural recovery by activating these pathways, offering potential new therapeutic options for SCI.