Depletion of SASH1, an astrocyte differentiation-related gene, contributes to functional recovery in spinal cord injury.

Abstract

AIMS:

This study aimed to evaluate the effects of the depletion of SAM and SH3 domain-containing protein 1 (SASH1) on functional recovery after spinal cord injury (SCI) and to investigate the possible mechanism of SASH1 knockdown in astrocytes facilitating axonal growth.

METHODS:

SCI model was established in adult rats. SASH1 small interfering RNA (siSASH1) was used to investigate its function. Hindlimb motor function was evaluated by the Basso-Bresnahan-Beattie (BBB) assay. The gene expressions were evaluated by the methods of qRT-PCR, Western-blotting, ELISA, and immunohistochemistry.

RESULTS:

SASH1 knockdown improved the BBB scores after SCI and significantly reduced GFAP expression. In cultured spinal astrocytes, siSASH1 treatment decreased interferon-γ release and increased brain-derived neurotrophic factor (BDNF) release. When cocultured with SASH1-knockdown astrocytes, axonal growth increased. The neuronal tropomyosin receptor kinase B (BDNF receptor) expression increased, especially in the axonal tips. SASH1 expression increased while NSCs differentiated into glial cells, instead of neurons. After SASH1 depletion, differentiated NSCs maintained a higher level of Nestin protein and an increase in BDNF release.

CONCLUSIONS:

These results indicate that SASH1 acts as an astrocytic differentiation-maintaining protein, and SASH1 downregulation limits glial activation and contributes toward functional recovery after SCI.

• Authors: Siyi Liu, Ge Lin, Qiao Yang, Penghui Wang, Chao Ma, Xiaowei Qian, Xiaomei He, Zhangji Dong, Yan Liu, Mei Liu, Ronghua Wu, Liu Yang
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 29 Issue 1 Pg. 228-238 (01 2023) ISSN: 1755-5949 [Electronic] England
• PMID: 36286186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Chemical References

• Brain-Derived Neurotrophic Factor
• RNA, Small Interfering
• Sash1 protein, rat
• Adaptor Proteins, Signal Transducing

Topics

• Animals
• Rats
• Astrocytes (metabolism)
• Brain-Derived Neurotrophic Factor (metabolism)
• Cell Differentiation
• Rats, Sprague-Dawley
• Recovery of Function (physiology)
• RNA, Small Interfering (genetics)
• Spinal Cord (metabolism)
• Spinal Cord Injuries (metabolism)
• Adaptor Proteins, Signal Transducing (genetics)