Department of Chemistry and the Beckman Institute for Advanced Science and Technology , University of Illinois at Urbana-Champaign , Urbana , Illinois 61801 , United States.
Chemistry Department , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States.
J Proteome Res. 2018 Apr 6;17(4):1463-1473. doi: 10.1021/acs.jproteome.7b00811. Epub 2018 Mar 20.
Conserved across vertebrates, the habenular nuclei are a pair of small symmetrical structures in the epithalamus. The nuclei functionally link the forebrain and midbrain by receiving input from and projecting to several brain regions. Each habenular nucleus comprises two major asymmetrical subnuclei, the medial and lateral habenula. These subnuclei are associated with different physiological processes and disorders, such as depression, nicotine addiction, and encoding aversive stimuli or omitting expected rewarding stimuli. Elucidating the functions of the habenular nuclei at the molecular level requires knowledge of their neuropeptide complement. In this work, three mass spectrometry (MS) techniques-liquid chromatography (LC) coupled to Orbitrap tandem MS (MS/MS), LC coupled to Fourier transform (FT)-ion cyclotron resonance (ICR) MS/MS, and matrix-assisted laser desorption/ionization (MALDI) FT-ICR MS-were used to uncover the neuropeptide profiles of the rodent medial and lateral habenula. With the assistance of tissue stabilization and bioinformatics, a total of 262 and 177 neuropeptides produced from 27 and 20 prohormones were detected and identified from the medial and lateral habenula regions, respectively. Among these neuropeptides, 136 were exclusively found in the medial habenula, and 51 were exclusively expressed in the lateral habenula. Additionally, novel sites of sulfation, a rare post-translational modification, on the secretogranin I prohormone are identified. The results demonstrate that these two small brain nuclei have a rich and differentiated peptide repertoire, with this information enabling a range of follow-up studies.
在脊椎动物中保守存在的缰核是一对位于上丘脑的小型对称结构。该核通过接收来自多个脑区的输入并投射到这些脑区，从而在大脑前脑和中脑之间建立功能连接。每个缰核由两个主要的不对称亚核组成，即内侧缰核和外侧缰核。这些亚核与不同的生理过程和疾病有关，如抑郁症、尼古丁成瘾以及编码厌恶刺激或忽略预期的奖励刺激。在分子水平上阐明缰核的功能需要了解其神经肽组成。在这项工作中，使用了三种质谱 (MS) 技术-液相色谱 (LC) 与轨道阱串联质谱 (MS/MS)、LC 与傅里叶变换 (FT)-离子回旋共振 (ICR) MS/MS 以及基质辅助激光解吸/电离 (MALDI) FT-ICR MS-来揭示啮齿动物内侧和外侧缰核的神经肽图谱。在组织稳定化和生物信息学的辅助下，共从内侧和外侧缰核区域检测和鉴定出 27 种和 20 种前激素产生的 262 种和 177 种神经肽。在这些神经肽中，有 136 种仅存在于内侧缰核，51 种仅存在于外侧缰核。此外，还鉴定到了分泌颗粒蛋白 I 前激素上罕见的翻译后修饰-硫酸化的新位点。这些结果表明，这两个小的脑核具有丰富且分化的肽谱，这些信息可以进行一系列后续研究。
