Regulation of cocaine- and amphetamine-regulated transcript-synthesising neurons of the hypothalamic paraventricular nucleus by endotoxin; implications for lipopolysaccharide-induced regulation of energy homeostasis.
Regulation of cocaine- and amphetamine-regulated transcript-synthesising neurons of the hypothalamic paraventricular nucleus by endotoxin; implications for lipopolysaccharide-induced regulation of energy homeostasis.
复制标题
内毒素对下丘脑室旁核可卡因和安非他明调节的转录合成神经元的调节；
DOI：
10.1111/j.1365-2826.2008.01758.x
复制
发表时间：
2008
影响因子：
3.2
通讯作者：
Lechan,RM
中科院分区：
文献类型：
--
作者：
Füzesi,T;Sánchez,E;Wittmann,G;Singru,PS;Fekete,C;Lechan,RM
传染病和细菌脂多糖（LPS）的施用会导致食物摄入量减少和能量消耗增加。由于下丘脑室旁核 (PVN) 在能量稳态调节中发挥着关键作用，并表达厌食肽、可卡因和安非他明调节转录物 (CART)，因此我们假设该核中 CART 合成的增加可能有助于 LPS 诱导的能量稳态变化。因此，我们通过半定量原位杂交研究了腹腔注射 LPS 对 PVN 中 CART 基因表达的影响。 LPS 导致 PVN 中 CART mRNA 水平快速增加。治疗一小时后，PVN 中银颗粒的密度增加了三倍，并在治疗后 3 小时仍保持较高水平。由于背侧迷走神经复合体是脑干中重要的植物中枢，受到含有 CART 的轴突的严重支配，因此我们确定了在将示踪剂立体定位注射到背侧迷走神经复合体后，逆行示踪剂霍乱毒素 B 亚基 (CTB) 是否在 PVN 的 CART 神经元中积聚。注射一周后，CTB 在 PVN 腹侧、内侧和外侧细小细胞分区的 CART 神经元中积聚。此外，LPS 诱导了 PVN 中投射到背侧迷走神经复合体的 CART 神经元群中的 c-fos 表达。这些数据表明，PVN 神经元中 CART 基因表达的增加可能导致 LPS 诱导的厌食症，并表明这种作用可能至少部分是通过 PVN-背侧迷走神经复合体途径介导的。
Infectious diseases and the administration of bacterial lipopolysaccharide (LPS) result in decreased food intake and increased energy expenditure. Because the hypothalamic paraventricular nucleus (PVN) has pivotal roles in the regulation of energy homeostasis and expresses an anorexic peptide, cocaine‐ and amphetamine‐regulated transcript (CART), we hypothesised that increased CART synthesis in this nucleus may contribute to LPS‐induced changes in energy homeostasis. Therefore, we studied the effects of intraperitoneal administration of LPS on CART gene expression in the PVN by semiquantitativein situhybridisation. LPS caused a rapid increase in CART mRNA levels in the PVN. One hour after treatment, the density of silver grains was increased by three‐fold in the PVN, and remained elevated 3 h after treatment. Because the dorsal vagal complex, an important vegetative centre in the brainstem, is heavily innervated by CART‐containing axons, we determined whether the retrograde tracer, cholera toxin B subunit (CTB), accumulates in CART neurons in the PVN following stereotaxic injection of the tracer into the dorsal vagal complex. One week after injection, CTB accumulated in CART neurons in the ventral, medial, and lateral parvocellular subdivisions of the PVN. In addition, LPS administration induced c‐fosexpression in a population of CART neurons in the PVN that project to the dorsal vagal complex. These data indicate that increased CART gene expression in neurons of PVN may contribute to LPS‐induced anorexia, and suggest that this action may be mediated, at least in part, through a PVN‐dorsal vagal complex pathway.