Psilopanagioti Aristea, Makrygianni Maria, Nikou Sofia, Logotheti Souzana, Papadaki Helen
Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Patras, Greece.
Department of Pathology, School of Medicine, University of Patras, Patras, Greece.
J Neuroendocrinol. 2020 Sep;32(9):e12899. doi: 10.1111/jne.12899. Epub 2020 Sep 9.
Feeding is a complex behaviour entailing elaborate interactions between forebrain, hypothalamic and brainstem neuronal circuits via multiple orexigenic and anorexigenic neuropeptides. Nucleobindin-2 (NUCB2)/nesfatin-1 is a negative regulator of food intake and body weight with a widespread distribution in rodent brainstem nuclei. However, its localisation pattern in the human brainstem is unknown. The present study aimed to explore NUCB2/nesfatin-1 immunoexpression in human brainstem nuclei and its possible correlation with body weight. Sections of human brainstem from 20 autopsy cases (13 males, seven females; eight normal weight, six overweight, six obese) were examined using immunohistochemistry and double immunofluorescence labelling. Strong immunoreactivity for NUCB2/nesfatin-1 was displayed in various brainstem areas, including the locus coeruleus, medial and lateral parabrachial nuclei, pontine nuclei, raphe nuclei, nucleus of the solitary tract, dorsal motor nucleus of vagus (10N), area postrema, hypoglossal nucleus, reticular formation, inferior olive, cuneate nucleus, and spinal trigeminal nucleus. NUCB2/nesfatin-1 was shown to extensively colocalise with neuropeptide Y and cocaine- and amphetamine-regulated transcript in the locus coeruleus, dorsal raphe nucleus and solitary tract. Interestingly, in the examined cases, NUCB2/nesfatin-1 protein expression was lower in obese than normal weight subjects in the solitary tract (P = 0.020). The findings of the present study provide neuroanatomical support for a role for NUCB2/nesfatin-1 in feeding behaviour and energy balance. The widespread distribution of NUCB2/nesfatin-1 in the human brainstem nuclei may be indicative of its pleiotropic effects on autonomic, neuroendocrine and behavioural processes. In the solitary tract, a key integrator of energy status, altered neurochemistry may contribute to obesity. Further research is necessary to decipher human brainstem energy homeostasis circuitry, which, despite its importance, remains inadequately characterised.
进食是一种复杂的行为，涉及前脑、下丘脑和脑干神经元回路之间通过多种促食欲和抑食欲神经肽进行的精细相互作用。核结合蛋白2（NUCB2）/nesfatin-1是食物摄入和体重的负调节因子，在啮齿动物脑干核中广泛分布。然而，其在人类脑干中的定位模式尚不清楚。本研究旨在探讨NUCB2/nesfatin-1在人类脑干核中的免疫表达及其与体重的可能相关性。使用免疫组织化学和双重免疫荧光标记检查了20例尸检病例（13例男性，7例女性；8例体重正常，6例超重，6例肥胖）的人类脑干切片。在包括蓝斑、臂旁内侧核和外侧核、脑桥核、中缝核、孤束核、迷走神经背运动核（10N）、最后区、舌下神经核、网状结构、下橄榄核、楔束核和三叉神经脊束核在内的各个脑干区域均显示出对NUCB2/nesfatin-1的强免疫反应性。在蓝斑、中缝背核和孤束中，NUCB2/nesfatin-1被证明与神经肽Y以及可卡因和苯丙胺调节转录肽广泛共定位。有趣的是，在所检查的病例中，孤束中肥胖受试者的NUCB2/nesfatin-1蛋白表达低于体重正常的受试者（P = 0.020）。本研究结果为NUCB2/nesfatin-1在进食行为和能量平衡中的作用提供了神经解剖学支持。NUCB2/nesfatin-1在人类脑干核中的广泛分布可能表明其对自主神经、神经内分泌和行为过程具有多效性作用。在作为能量状态关键整合器的孤束中，神经化学改变可能导致肥胖。尽管其很重要，但仍需进一步研究来破译人类脑干能量稳态回路，目前该回路的特征仍不充分。
