Enriched environment promotes post-stroke neurogenesis through NF-kappa B-mediated secretion of IL-17A from astrocytes
Enriched environment promotes post-stroke neurogenesis through NF-kappa B-mediated secretion of IL-17A from astrocytes
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丰富的环境通过 NF-κB 介导的星形胶质细胞分泌 IL-17A 促进中风后神经发生。
DOI：
10.1016/j.brainres.2018.02.030
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发表时间：
2018
期刊：
影响因子：
2.9
通讯作者：
Zhang Jiancheng
中科院分区：
文献类型：
--
作者：
Zhang Yujing;Xu Dan;Qi Hong;Yuan Yin;Liu Hong;Yao Shanglong;Yuan Shiying;Zhang Jiancheng
丰富的环境（EE）已被证明可以促进中风后神经发生和功能恢复。然而，潜在的分子机制仍然知之甚少。雄性C57 BL/6小鼠大脑中动脉闭塞（MCAO）60 min后再灌注，在标准环境（SE）或EE中饲养，发现缺血后28 d EE细胞质核因子κ B（NF-κ B）/p65蛋白水平降低，细胞核NF-κ B/p65蛋白表达增加。然而，缺血后EE对缺血半球28 dpi的末端脱氧核苷酸转移酶生物素-dUTP缺口末端标记（TUNEL）阳性细胞无影响。用NF-kB抑制剂Bay11 - 7082治疗的EE小鼠在28 dpi中风后具有降低的室管膜下区（SVZ）神经前体细胞（NPC）增殖、神经元分化和随后的功能恢复。Bay11 - 7082处理减弱了缺血后EE对28dpi时白细胞介素17A（IL-17A）mRNA和蛋白表达的促进作用。此外，我们的体外数据显示，在原代星形胶质细胞培养物中加入Bay11 - 7082显著降低了活化星形胶质细胞的细胞裂解物和培养上清液中IL-17 A的表达。用中和抗体阻断IL-17 A可消除EE对SVZ来源的NPC增殖、神经元分化和随后的卒中后功能恢复的促进作用。因此，我们的研究结果揭示了NF-κ B/IL-17 A信号通路在EE介导的缺血性卒中后神经发生和功能恢复中的先前未表征的性质。
Enriched environment (EE) has been shown to promote post-stroke neurogenesis and functional recovery. However, the underlying molecular mechanisms remains poorly understood. Male C57BL/6 mice underwent 60-min middle cerebral artery occlusion (MCAO) followed by reperfusion, after which mice were housed in either standard environment (SE) or EE. We found that post-ischemic EE exhibited reduced protein level of nuclear factor κB (NF-κB)/p65 in cytoplasm and increased its expression correspondingly in nucleus at 28 days post-ischemia (dpi). However, post-ischemic EE had no effects on terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL)-positive cells in ischemic hemisphere at 28dpi. EE mice treated with NF-kB inhibitor Bay11-7082 had decreased subventricular zone (SVZ) neural precursor cells (NPCs) proliferation, neuronal differentiation and subsequent functional recovery after stroke at 28dpi. Bay11-7082 treatment attenuated the promoting effects of post-ischemic EE on interleukin 17A (IL-17A) messenger RNA (mRNA) and protein expression at 28dpi. Furthermore, ourin vitrodata revealed that in primary astrocyte cultures addition of Bay11-7082 markedly decreased the expression of IL-17A in both the cell lysate and culture supernatant of activated astrocytes. Blockade of IL-17A with neutralizing antibody abrogated the promoting role of EE in NPCs proliferation derived from SVZ, neuronal differentiation and subsequent functional recovery after stroke. Thus, our results reveal a previously uncharacterized property of NF-κB/IL-17A signaling pathway in EE-mediated neurogenesis and functional recovery after ischemic stroke.