LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone
LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone
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LXR激动剂挽救了地塞米松诱导的小脑颗粒细胞增殖缺陷
DOI：
10.1016/j.bbrc.2016.06.142
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发表时间：
2016
影响因子：
3.1
通讯作者：
Fan Xiaotang
中科院分区：
文献类型：
--
作者：
Bian Xuting;Zhong Hongyu;Li Fen;Cai Yulong;Li Xin;Wang Lian;Fan Xiaotang
在出生后早期暴露于地塞米松（DEX）会导致永久性神经运动和智力缺陷，并阻碍小脑生长。肝脏X受体（LXR）在中枢神经系统发育中起重要作用。然而，LXR对DEX介导的小脑发育障碍的影响尚未确定。因此，小鼠用LXR激动剂TO901317（TO）预处理，随后暴露于DEX以评估其对小脑发育期间DEX介导的缺陷的保护作用。结果表明，出生后7天急性接触DEX导致小脑发育明显受损，小脑外颗粒层颗粒神经元前体细胞增殖减少。TO预处理可减弱这种效应。我们进一步发现，DEX引起的增殖下降是通过上调糖皮质激素受体和p27 kip1而发生的，LXR激动剂预处理可以部分阻止这种情况。总体而言，我们的研究结果表明，LXR激动剂预处理可以防止DEX诱导的出生后小鼠小脑发育缺陷，因此可能被招募来抵消这种GC副作用。
Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.