Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, no. 268, 800 Washington Street, Boston, Massachusetts 02111, USA.
Endocrinology. 2012 Aug;153(8):3804-14. doi: 10.1210/en.2012-1235. Epub 2012 Jun 14.
We previously demonstrated that refeeding after a prolonged fast activates a subset of neurons in the ventral parvocellular subdivision of the paraventricular nucleus (PVNv) as a result of increased melanocortin signaling. To determine whether these neurons contribute to satiety by projecting to the nucleus tractus solitarius (NTS), the retrogradely transported marker substance, cholera toxin-β (CTB), was injected into the dorsal vagal complex of rats that were subsequently fasted and refed for 2 h. By double-labeling immunohistochemistry, CTB accumulation was found in the cytoplasm of the majority of refeeding-activated c-Fos neurons in the ventral parvocellular subdivision of the hypothalamic paraventricular nucleus (PVNv). In addition, a large number of refeeding-activated c-Fos-expressing neurons were observed in the lateral parvocellular subdivision (PVNl) that also contained CTB and were innervated by axon terminals of proopiomelanocortin neurons. To visualize the location of neuronal activation within the NTS by melanocortin-activated PVN neurons, α-MSH was focally injected into the PVN, resulting in an increased number of c-Fos-containing neurons in the PVN and in the NTS, primarily in the medial and commissural parts. All refeeding-activated neurons in the PVNv and PVNl expressed the mRNA of the glutamatergic marker, type 2 vesicular glutamate transporter (VGLUT2), indicating their glutamatergic phenotype, but only rare neurons contained oxytocin. These data suggest that melanocortin-activated neurons in the PVNv and PVNl may contribute to refeeding-induced satiety through effects on the NTS and may alter the sensitivity of NTS neurons to vagal satiety inputs via glutamate excitation.
我们之前的研究表明，长时间禁食后再喂食会激活室旁核腹侧小细胞亚区（PVNv）中的一部分神经元，这是由于黑素皮质素信号的增加。为了确定这些神经元是否通过投射到孤束核（NTS）来促进饱腹感，将逆行转运示踪剂霍乱毒素-β（CTB）注入禁食后再喂食 2 小时的大鼠的迷走神经复合体。通过双重免疫组织化学标记，发现 CTB 积聚在大多数再喂食激活的 c-Fos 神经元的细胞质中，这些神经元位于下丘脑室旁核的腹侧小细胞亚区（PVNv）。此外，在外侧小细胞亚区（PVNl）中也观察到大量再喂食激活的 c-Fos 表达神经元，这些神经元含有 CTB，并被前阿黑皮素原神经元的轴突末梢支配。为了通过黑素皮质素激活的 PVN 神经元在 NTS 内可视化神经元激活的位置，将 α-MSH 局部注射到 PVN 中，导致 PVN 和 NTS 中 c-Fos 阳性神经元的数量增加，主要位于内侧和连合部。PVNv 和 PVNl 中的所有再喂食激活神经元都表达谷氨酸能标志物 2 型囊泡谷氨酸转运体（VGLUT2）的 mRNA，表明它们具有谷氨酸能表型，但只有少数神经元含有催产素。这些数据表明，PVNv 和 PVNl 中的黑素皮质素激活神经元可能通过对 NTS 的作用来促进再喂食诱导的饱腹感，并通过谷氨酸兴奋改变 NTS 神经元对迷走神经饱腹感输入的敏感性。
