Inflammatory Factor IL1αInduces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca^(2+)/CaMK2b Pathway  

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

机构地区：[1]Scientific Research Center,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,518107,China [2]Department of Gynecology,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,518107,China [3]Pelvic Floor Disorders Center,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,518107,China [4]Big Data Center,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,518107,China [5]Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou,310016,China [6]Orthopaedic and Neurological Repair Center,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,518107,China

出　　处：《Neuroscience Bulletin》2024年第4期421-438,共18页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82071362,82002899);the Basic Research Project of Shenzhen Science and Technology Innovation Commission(JCYJ202205303001577,JCYJ20190809165201646);Basic Research Projects of Shenzhen Science and Technology Program(JCYJ20180307150610733).

摘　　要：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 Ca^(2+)transport functions were inhibited in astrocytes after SCI.Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in vitro.By screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage model.Blockade of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI.Overall,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.

关 键 词：IL1α Grin2c ASTROCYTE Spinal cord injury 

分 类 号：R741.02[医药卫生—神经病学与精神病学]