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

Spinal Cord volume 63, pages 263–269 (2025)Cite this article

Subjects

Abstract

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.

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Fig. 1: Astrocytes landscape in SCI.
Fig. 2: BDNF regulation of GABA neurotransmission and GABA receptor signaling in astrocytes contribute to neuron regeneration.
Fig. 3: hUC-MSCs promote neuron regeneration by activating the BDNF regulation of GABA neurotransmission of astrocyte.
Fig. 4: iPS-derived MSC enhance neural regeneration through BDNF, GABA and GABA receptor signaling of astrocyte.

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Data availability

Data sources and handling of the publicly available datasets used in this study are described in the Materials and Methods. All source code developed for this study is proprietary and cannot be shared publicly. However, researchers interested in accessing the code for non-commercial purposes may contact the corresponding author, Yifeng Sun, at syf498054232@163.com.

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Funding

This work was supported by National Natural Science Foundation of China (81702667), and China Postdoctoral Science Foundation (8206300728).

Author information

Authors and Affiliations

  1. Department of Spine Surgery, Yantaishan Hospital, Binzhou Medical University, 10087 Science and Technology Avenue, Yantai, Shandong, 264003, P. R. China

    Qingsheng Zhou

  2. MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, 100871, P. R. China

    Qiongxuan Fang

  3. Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250014, P. R. China

    Chunming Zhang & Wei Liu

  4. Orthopaedic and Sports Medicine Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing，102218, P. R. China

    Yifeng Sun

Authors
  1. Qingsheng Zhou
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  2. Qiongxuan Fang
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  3. Chunming Zhang
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  4. Wei Liu
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  5. Yifeng Sun
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Contributions

YS conceived the study and generated figures and wrote the manuscript, QZ collected and analysed the data, QF performed a part of data analysis. CZ and WL help to generated figures. All authors reviewed the manuscript.

Corresponding author

Correspondence to Yifeng Sun.

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Competing interests

The authors declare no competing interests.

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This is a bioinformatic analysis; therefore, ethics approval and consent to participate are not applicable.

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Zhou, Q., Fang, Q., Zhang, C. et al. BDNF-GABA signaling in astrocytes: enhancing neural repair after SCI through MSC therapies. Spinal Cord 63, 263–269 (2025). https://doi.org/10.1038/s41393-025-01077-x

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