Depletion of Astrocytic Transglutaminase 2 Improves Injury Outcomes

Mol Cell Neurosci, 2018 · DOI: 10.1016/j.mcn.2018.06.007 · Published: October 1, 2018

Simple Explanation

Astrocytes, a type of brain cell, are crucial for supporting neurons. After an injury to the central nervous system (CNS), astrocytes react, changing their behavior, which can be both helpful and harmful. This study focuses on transglutaminase 2 (TG2), a protein that affects cell survival. The research shows that when TG2 is reduced in astrocytes, the astrocytes become better at protecting neurons from injury caused by oxygen and glucose deprivation. This improvement involves changes in genes related to the structure around cells and nerve growth. In mice with spinal cord injuries, reducing TG2 in astrocytes also resulted in less scar tissue formation. This suggests that TG2 plays a key role in how astrocytes react after a CNS injury, potentially by affecting pathways that promote cell survival.

Study Duration

Not specified

Participants

Mice, Sprague Dawley rats

Evidence Level

In vitro and in vivo study

Key Findings

1
Knocking down TG2 in astrocytes increases their ability to protect neurons from oxygen glucose deprivation/reperfusion injury.
2
TG2 deletion in astrocytes leads to the upregulation of pro-survival/pro-regenerative genes, including BDNF, Decorin (DCN) and Adamts6.
3
Ablation of astrocytic TG2 attenuates astrogliosis, indicated by reduced GFAP expression, following in vivo CNS injury in mice subjected to a spinal cord injury.

Research Summary

This study investigates the role of astrocytic transglutaminase 2 (TG2) in CNS injury outcomes. It demonstrates that reducing TG2 in astrocytes enhances their neuroprotective capabilities in vitro, particularly against oxygen-glucose deprivation. Transcriptome analysis reveals that TG2 deletion upregulates genes involved in axonal outgrowth and ECM remodeling, suggesting a shift towards a pro-survival phenotype. This is associated with increased cJun/AP-1 activation. In vivo experiments show that astrocyte-specific TG2 deletion attenuates astrogliosis following spinal cord injury in mice, further supporting the notion that TG2 plays a critical role in mediating reactive astrocyte properties.

Practical Implications

Therapeutic Target

TG2 could be a potential therapeutic target for CNS injuries.

Neuroprotection Strategies

Modulating astrocytic TG2 levels may enhance neuroprotection in CNS injuries.

Scarring Reduction

Targeting TG2 could reduce detrimental scar formation after spinal cord injury.

Study Limitations

1
Specific signaling mechanisms by which astrocytic TG2 mediates its effects need further elucidation.
2
Long-term functional outcomes following spinal cord injury were not assessed.
3
The study focuses primarily on in vitro and early in vivo changes (3 days post-injury).

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