LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice.
LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice.
复制标题
DOI：
10.1186/s12974-022-02423-z
复制
发表时间：
2022-02-26
影响因子：
9.3
通讯作者：
Mansuy-Aubert V
中科院分区：
文献类型：
--
作者：
Gavini CK;Elshareif N;Aubert G;Germanwala AV;Calcutt NA;Mansuy-Aubert V
周围神经病变是老年人中常见的进行性疾病，干扰日常活动。寻找有效的治疗方法来治疗或延缓这种与年龄相关的神经退行性变具有重要意义。通过减少泡沫巨噬细胞沉默巨噬细胞显示出对老年小鼠外周神经中与年龄相关的退行性变化的显著改善。我们以前证明了胆固醇传感器肝脏X受体（LXR）与强效激动剂GW3965的激活，在饮食诱导的肥胖模型中减轻疼痛。我们试图测试LXR激活是否可以改善老年小鼠的神经病变。用GW 3965（25 mg/Kg体重）处理21月龄小鼠3个月，同时测试机械异常性疼痛和热痛觉过敏。在终止时，使用流式细胞术分析背根神经节和坐骨神经细胞。分选免疫细胞并分析胆固醇和基因表达。分析爪皮肤的神经纤维。还对一些人腓肠神经进行了评价。使用t检验或单因素方差分析进行比较。GW 3965治疗可以防止老年小鼠随着时间的推移出现机械超敏反应和热痛觉过敏。我们还观察到坐骨神经巨噬细胞的极化和胆固醇含量的变化，伴随着皮肤神经纤维的显着增加。这些结果表明，激活LXR可能通过改变神经免疫细胞脂质含量来延缓PNS衰老。我们的研究为治疗或延缓衰老过程中的神经病变提供了新的潜在靶点。在线版本包含补充材料，可通过10.1186/s12974 - 022 - 02423-z获得。
Peripheral neuropathy is a common and progressive disorder in the elderly that interferes with daily activities. It is of importance to find efficient treatments to treat or delay this age-related neurodegeneration. Silencing macrophages by reducing foamy macrophages showed significant improvement of age-related degenerative changes in peripheral nerves of aged mice. We previously demonstrated that activation of the cholesterol sensor Liver X receptor (LXR) with the potent agonist, GW3965, alleviates pain in a diet-induced obesity model. We sought to test whether LXR activation may improve neuropathy in aged mice. 21-month-old mice were treated with GW3965 (25 mg/Kg body weight) for 3 months while testing for mechanical allodynia and thermal hyperalgesia. At termination, flow cytometry was used to profile dorsal root ganglia and sciatic nerve cells. Immune cells were sorted and analyzed for cholesterol and gene expression. Nerve fibers of the skin from the paws were analyzed. Some human sural nerves were also evaluated. Comparisons were made using either t test or one-way ANOVA. Treatment with GW3965 prevented the development of mechanical hypersensitivity and thermal hyperalgesia over time in aged mice. We also observed change in polarization and cholesterol content of sciatic nerve macrophages accompanied by a significant increase in nerve fibers of the skin. These results suggest that activation of the LXR may delay the PNS aging by modifying nerve-immune cell lipid content. Our study provides new potential targets to treat or delay neuropathy during aging. The online version contains supplementary material available at 10.1186/s12974-022-02423-z.
登录
查看更多内容
影响因子：
4
作者：
Gibson MS;Domingues N;Vieira OV
通讯作者：
Vieira OV
影响因子：
1.8
作者：
Bala U;Tan KL;Ling KH;Cheah PS
通讯作者：
Cheah PS
影响因子：
4.6
作者：
Gavini, Chaitanya K.;Bonomo, Raiza;Mansuy-Aubert, Virginie
通讯作者：
Mansuy-Aubert, Virginie
影响因子：
13.6
作者：
Hanewinckel R;van Oijen M;Ikram MA;van Doorn PA
通讯作者：
van Doorn PA
影响因子：
3.3
作者：
Defrancesco-Lisowitz, A.;Lindborg, J. A.;Niemi, J. P.;Zigmond, R. E.
通讯作者：
Zigmond, R. E.