Galectin-3 causes enteric neuronal loss in mice after left sided permanent middle cerebral artery occlusion, a model of stroke.
Galectin-3 causes enteric neuronal loss in mice after left sided permanent middle cerebral artery occlusion, a model of stroke.
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DOI：
10.1038/srep32893
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发表时间：
2016-09-09
影响因子：
4.6
通讯作者：
Voss U
中科院分区：
文献类型：
--
作者：
Cheng X;Boza-Serrano A;Turesson MF;Deierborg T;Ekblad E;Voss U
除了脑损伤外，中风患者还经常患有胃肠道并发症。涉及半乳糖凝集素-3的神经免疫相互作用，从大脑中的小胶质细胞释放，介导中风后促炎反应。我们研究了中风对肠神经系统的可能后果和半乳糖凝集素-3的参与。我们发现，永久性大脑中动脉闭塞（pMCAO）诱导半乳糖凝集素-3+/+小鼠回肠和结肠肠神经元的损失，但在半乳糖凝集素-3-/-小鼠中没有。在体外实验中，我们发现来自半乳糖凝集素-3 +/+的血清，而不是来自半乳糖凝集素-3-/-的血清，pMCAO小鼠，导致C57 BL/6 J肌间神经元的损失，而来自TLR 4-/-小鼠的肌间神经元不受影响。进一步纯化的半乳糖凝集素-3（10−6 M）导致培养的C57 BL/6 J肌间神经元丢失。转化生长因子β激活激酶1（TAK 1）或AMP激活激酶（AMPK）的抑制剂在体外抵消纯化的半乳糖凝集素3和半乳糖凝集素3+/+ pMCAO血清诱导的损失。结合我们表明，中风（pMCAO）触发中枢和外周半乳糖凝集素-3释放，通过TLR 4介导的涉及TAK 1和AMPK的机制引起肠神经元损失。半乳糖凝集素-3被认为是治疗脑卒中后并发症的靶点。
In addition to brain injury stroke patients often suffer gastrointestinal complications. Neuroimmune interactions involving galectin-3, released from microglia in the brain, mediates the post-stroke pro-inflammatory response. We investigated possible consequences of stroke on the enteric nervous system and the involvement of galectin-3. We show that permanent middle cerebral artery occlusion (pMCAO) induces loss of enteric neurons in ileum and colon in galectin-3+/+, but not in galectin-3−/−, mice. In vitro we show that serum from galectin-3+/+, but not from galectin-3−/−, mice subjected to pMCAO, caused loss of C57BL/6J myenteric neurons, while myenteric neurons derived from TLR4−/− mice were unaffected. Further purified galectin-3 (10−6 M) caused loss of cultured C57BL/6J myenteric neurons. Inhibitors of transforming growth factor β-activated kinase 1 (TAK1) or AMP activated kinase (AMPK) counteracted both the purified galectin-3 and the galectin-3+/+ pMCAO serum-induced loss in vitro. Combined we show that stroke (pMCAO) triggers central and peripheral galectin-3 release causing enteric neuronal loss through a TLR4 mediated mechanism involving TAK1 and AMPK. Galectin-3 is suggested a target for treatment of post-stroke complications.
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