Inflammatory Factor IL1α Induces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca2+/CaMK2b Pathway.

Yu Xia, Lu Ding, Changlin Zhang, Qi Xu, Ming Shi, Tianshun Gao, Feng-Quan Zhou, David Y B Deng

Neuroscience bulletin 2024 Apr

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Spinal cord injury (SCI) is one of the most devastating traumas, and the aberrant proliferation of astrocytes usually causes neurological deficits. However, the mechanism underlying astrocyte over-proliferation after SCI is unclear. Grin2c (glutamate ionotropic receptor type 2c) plays an essential role in cell proliferation. Our bioinformatic analysis indicated that Grin2c and Ca2+ transport functions were inhibited in astrocytes after SCI. Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca2+/calmodulin-dependent protein kinase 2b (CaMK2b) pathway in vitro. By screening different inflammatory factors, interleukin 1α (IL1α) was further found to inhibit Grin2c/Ca2+/CaMK2b and enhance astrocyte proliferation in an oxidative damage model. Blockade of IL1α using neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI. Overall, this study suggests that IL1α promotes astrocyte proliferation by suppressing the Grin2c/Ca2+/CaMK2b pathway after SCI, revealing a novel pathological mechanism of astrocyte proliferation, and may provide potential targets for SCI repair. © 2023. The Author(s).

Citation

Yu Xia, Lu Ding, Changlin Zhang, Qi Xu, Ming Shi, Tianshun Gao, Feng-Quan Zhou, David Y B Deng. Inflammatory Factor IL1α Induces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca2+/CaMK2b Pathway. Neuroscience bulletin. 2024 Apr;40(4):421-438