Neuronal LXR Regulates Neuregulin 1 Expression and Sciatic Nerve-Associated Cell Signaling in Western Diet-fed Rodents
Neuronal LXR Regulates Neuregulin 1 Expression and Sciatic Nerve-Associated Cell Signaling in Western Diet-fed Rodents
复制标题
DOI：
10.1038/s41598-020-63357-1
复制
发表时间：
2020-04-14
影响因子：
4.6
通讯作者：
Mansuy-Aubert, Virginie
中科院分区：
文献类型：
--
作者：
Gavini, Chaitanya K.;Bonomo, Raiza;Mansuy-Aubert, Virginie
由周围神经损伤引起的神经病理性疼痛显著影响感觉知觉和生活质量。越来越多的证据表明，胆固醇与肥胖和糖尿病相关神经病变的发生和进展密切相关。然而，周围神经系统（PNS）胆固醇/脂质代谢如何参与神经病发病机制的确切机制仍知之甚少。LXR通路的失调已经在许多神经病模型中被鉴定。在感觉神经元中表达的胆固醇传感器LXR α/β对于适当的外周神经功能是必需的。感觉神经元中LXR α/β的缺失导致疼痛样行为。在这项研究中，我们确定了在感觉神经元中表达的LXR α/β调节神经元Neuregulin 1（Nrg 1），这是一种参与细胞间通讯的蛋白质。使用体内细胞特异性方法，我们观察到感觉神经元LXR的缺失改变了位于坐骨神经中的非神经元细胞（可能代表雪旺细胞（SC））中的基因。我们的数据表明，神经元LXRs可能通过Nrg 1依赖性机制调节非神经元细胞功能。WD喂养小鼠DRG神经元中Nrg 1表达的减少可能表明肥胖症中Nrg 1依赖性神经元-SC通讯的改变。神经元和非神经元细胞如SC之间的通讯可能是研究和理解肥胖相关神经病变和PNS功能障碍的分子和细胞机制的新的生物学途径。
Neuropathic pain caused by peripheral nerve injuries significantly affects sensory perception and quality of life. Accumulating evidence strongly link cholesterol with development and progression of Obesity and Diabetes associated-neuropathies. However, the exact mechanisms of how cholesterol/lipid metabolism in peripheral nervous system (PNS) contributes to the pathogenesis of neuropathy remains poorly understood. Dysregulation of LXR pathways have been identified in many neuropathic models. The cholesterol sensor, LXR alpha/beta, expressed in sensory neurons are necessary for proper peripheral nerve function. Deletion of LXR alpha/beta from sensory neurons lead to pain-like behaviors. In this study, we identified that LXR alpha/beta expressed in sensory neurons regulates neuronal Neuregulin 1 (Nrg1), protein involved in cell-cell communication. Using in vivo cell-specific approaches, we observed that loss of LXR from sensory neurons altered genes in non-neuronal cells located in the sciatic nerve (potentially representing Schwann cells (SC)). Our data suggest that neuronal LXRs may regulate non-neuronal cell function via a Nrg1-dependent mechanism. The decrease in Nrg1 expression in DRG neurons of WD-fed mice may suggest an altered Nrg1-dependent neuron-SC communication in Obesity. The communication between neurons and non-neuronal cells such as SC could be a new biological pathway to study and understand the molecular and cellular mechanism underlying Obesity-associated neuropathy and PNS dysfunction.