DISTRIBUTION AND NEUROPEPTIDE COEXISTENCE OF NUCLEOBINDIN-2 mRNA/NESFATIN-LIKE IMMUNOREACTIVITY IN THE RAT CNS
DISTRIBUTION AND NEUROPEPTIDE COEXISTENCE OF NUCLEOBINDIN-2 mRNA/NESFATIN-LIKE IMMUNOREACTIVITY IN THE RAT CNS
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DOI：
10.1016/j.neuroscience.2008.07.054
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发表时间：
2008-10-15
期刊：
影响因子：
3.3
通讯作者：
Broberger, C.
中科院分区：
文献类型：
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作者：
Foo, K. S.;Brismar, H.;Broberger, C.
最近发现nesfatin-1蛋白片段与控制食物摄入有关。该片段的中枢给药导致厌食和体重增加减少，而反义或免疫nesfatin-1拮抗作用导致食物摄入增加和超重。Nesfatin-1来源于前体核结合素-2（NUCB 2）。为了确定NUCB 2/nesfatin-1的分解代谢作用的神经回路基础，我们已经使用原位杂交和免疫组织化学来映射这种蛋白质及其mRNA在大鼠中枢神经系统中的分布，并进行双标记实验，以定位其表达功能定义的神经元群体。这些实验证实了先前的观察结果，但也提出了几种新的NUCB 2细胞群。NUCB 2 mRNA和nesfatin样免疫反应性最集中在下丘脑，在视上核，室旁核，室周核和弓状核和外侧下丘脑区/穹窿周围区。此外，在下丘脑外，在丘脑束旁核、Edinger-Westphal核、蓝斑、腹侧中缝系统、孤束核和脊髓的节前交感中间外侧细胞柱以及垂体前叶和中间叶中观察到标记。在神经元中，免疫反应性几乎完全局限于胞体和初级树突，几乎没有轴突终末的标记。双标记免疫组化显示nesfatin与加压素和催产素在大细胞神经内分泌神经元，促甲状腺激素释放激素，促肾上腺皮质激素释放激素，生长抑素，神经降压素和生长激素释放激素在小细胞神经内分泌神经元，前阿黑皮素（但不是神经肽Y）在弓状核和黑色素浓缩激素（但不是下丘脑）在外侧下丘脑的共定位。此外，nesfatin与可卡因和安非他明调节的转录物在几乎所有NUCB 2表达的脑区广泛共定位。这些数据揭示了NUCB 2/nesfatin-1的分布比以前已知的更广泛，表明这种蛋白质的代谢作用不仅涉及摄食行为，还涉及内分泌和自主神经对能量消耗的影响。此外，nesfatin样免疫反应性的亚细胞分布表明，这种蛋白质可能不像传统的分泌型神经调节剂。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The protein fragment nesfatin-1 was recently implicated in the control of food intake. Central administration of this fragment results in anorexia and reduced body weight gain, whereas antisense or immunological nesfatin-1 antagonism causes increased food intake and overweight. Nesfatin-1 is derived from the precursor nucleobindin-2 (NUCB2). To identify the neurocircuitry underpinning the catabolic effects of NUCB2/nesfatin-1, we have used in situ hybridization and immunohistochemistry to map the distribution of this protein and its mRNA in the rat CNS and performed double-labeling experiments to localize its expression to functionally defined neuronal populations. These experiments confirm previous observations but also present several novel NUCB2 cell populations. Both NUCB2 mRNA and nesfatin-like immunoreactivity was most concentrated in the hypothalamus, in the supraoptic, paraventricular, periventricular and arcuate nuclei and the lateral hypothalamic area/perifornical region. Additionally, outside of the hypothalamus, labeling was observed in the thalamic parafascicular nucleus, the Edinger-Westphal nucleus, locus coeruleus, ventral raphe system, nucleus of solitary tract and in the preganglionic sympathetic intermediolateral cell column of the spinal cord, and the pituitary anterior and intermediate lobes. In neurons, immunoreactivity was almost exclusively confined to perikarya and primary dendrites with virtually no labeling of axonal terminals. Double-labeling immunohistochemistry revealed colocalization of nesfatin with vasopressin and oxytocin in magnocellular neuroendocrine neurons, thyrotropin-releasing hormone, corticotropin-releasing hormone, somatostatin, neurotensin, and growth-hormone-releasing hormone in parvocellular neuroendocrine neurons, pro-opiomelanocortin (but not neuropeptide Y) in the arcuate nucleus and melanin-concentrating hormone (but not hypocretin) in the lateral hypothalamus. Furthermore, nesfatin was extensively colocalized with cocaine- and amphetamine-regulated transcript in almost all NUCB2-expressing brain regions. These data reveal a wider distribution of NUCB2/nesfatin-1 than previously known, suggesting that the metabolic actions of this protein may involve not only feeding behavior but also endocrine and autonomic effects on energy expenditure. In addition, the subcellular distribution of nesfatin-like immunoreactivity indicates that this protein may not be processed like a conventional secreted neuromodulator. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.