Osteopontin expression in acute immune response mediates hippocampal synaptogenesis and adaptive outcome following cortical brain injury.
Osteopontin expression in acute immune response mediates hippocampal synaptogenesis and adaptive outcome following cortical brain injury.
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急性免疫反应中骨桥蛋白的表达介导皮质脑损伤后的海马突触发生和适应性结果。
DOI：
10.1016/j.expneurol.2014.08.015
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发表时间：
2014-11
影响因子：
5.3
通讯作者：
Phillips, Linda L.
中科院分区：
文献类型：
--
作者：
Chan, Julie L.;Reeves, Thomas M.;Phillips, Linda L.
Traumatic brain injury (TBI) produces axotomy, deafferentation and reactive synaptogenesis. Inflammation influences synaptic repair, and the novel brain cytokine osteopontin (OPN) has potential to support axon regeneration through exposure of its integrin receptor binding sites. This study explored whether OPN secretion and proteolysis by matrix metalloproteinases (MMPs) mediate the initial degenerative phase of synaptogenesis, targeting reactive neuroglia to affect successful repair. Adult rats received unilateral entorhinal cortex lesion (UEC) modeling adaptive synaptic plasticity. Over the first week postinjury, hippocampal OPN protein and mRNA were assayed and histology performed. At 1–2d, OPN protein increased up to 51 fold, and was localized within activated, mobilized glia. OPN transcript also increased over 50 fold, predominantly within reactive microglia. OPN fragments known to be derived from MMP proteolysis were elevated at 1d, consistent with prior reports of UEC glial activation and enzyme production. Postinjury minocycline immunosuppression attenuated MMP-9 gelatinase activity, which was correlated with reduction of neutrophil gelatinase-associated lipocalin (LCN2) expression, and reduced OPN fragment generation. The antibiotic also attenuated removal of synapsin-1 positive axons from the deafferented zone. OPN KO mice subjected to UEC had similar reduction of hippocampal MMP-9 activity, as well as lower synapsin-1 breakdown over the deafferented zone. MAP1B and N-cadherin, surrogates of cytoarchitecture and synaptic adhesion, were not affected. OPN KO mice with UEC exhibited time dependent cognitive deficits during the synaptogenic phase of recovery. This study demonstrates that OPN can mediate immune response during TBI synaptic repair, positively influencing synapse reorganization and functional recovery.
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脑膜免疫调节学习和记忆：IL-4 的关键作用。
影响因子：
15.3
作者：
Derecki, Noel C.;Cardani, Amber N.;Yang, Chun Hui;Quinnies, Kayla M.;Crihfield, Anastasia;Lynch, Kevin R.;Kipnis, Jonathan
通讯作者：
Kipnis, Jonathan
影响因子：
2.7
作者：
ENNACEUR, A;DELACOUR, J
通讯作者：
DELACOUR, J
影响因子：
5.6
作者：
Borges, Karin;Gearing, Maria;Dingledine, Raymond
通讯作者：
Dingledine, Raymond
影响因子：
4.8
作者：
Fifre, A;Sponne, I;Pillot, T
通讯作者：
Pillot, T
影响因子：
4.7
作者：
Baratz R;Tweedie D;Rubovitch V;Luo W;Yoon JS;Hoffer BJ;Greig NH;Pick CG
通讯作者：
Pick CG