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.