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中缝背核内 nesfatin-1 通过 5-HT 神经元影响雄性母爱剥夺大鼠的内脏敏感性。

Nesfatin-1 in the dorsal raphe nucleus influences visceral sensitivity via 5-HT neurons in male maternally separated rats.

机构信息

Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China.

Department of Gastroenterology, Jingjiang People's Hospital, Jingjiang, Jiangsu Province, 214500, China.

出版信息

Sci Rep. 2018 Jun 19;8(1):9334. doi: 10.1038/s41598-018-27592-x.

DOI:10.1038/s41598-018-27592-x
PMID:29921870
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6008476/
Abstract

Nesfatin-1, a satiety molecule processed from nucleobindin2 (NUCB2), is implicated in visceral hypersensitivity in rats and colocalized with 5-hydroxytryptamine (5-HT) in the dorsal raphe nucleus (DRN). Maternal separation (MS) in rats contributes to visceral hypersensitivity via elevated expression of 5-HT in the DRN. Intracerebroventricular injection of nesfatin-1 activates DRN 5-HT neurons. In this study, A model of visceral hypersensitivity was developed by subjecting rats to MS. Colorectal distension was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR) scores and electromyogram (EMG) magnitude. MS rats exhibited higher AWR scores and EMG magnitude compared with controls. The numbers of nesfatin-1- and tryptophan hydroxylase (TPH, the rate-limiting enzyme for 5-HT synthesis)-positive cells in the DRN were significantly elevated accordingly. Visceral hypersensitivity was significantly alleviated in MS rats treated with intra-DRN administration of anti-nesfatin-1/NUCB2, accompanied by decreased expression of 5-HT and TPH in the DRN, compared with the vehicle-treated group. In contrast, intra-DRN administration of nesfatin-1 into normal adult rats induced visceral hypersensitivity, which correlated with elevated expression of 5-HT and TPH in the DRN. In conclusion, Nesfatin-1 has critical effects on visceral hypersensitivity; the underlying mechanisms might be related to the activation of DRN 5-HT neurons.

摘要

内脂素-1 是一种从核结合蛋白 2（NUCB2）加工而来的饱腹感分子，与背侧中缝核（DRN）中的 5-羟色胺（5-HT）共定位，与大鼠内脏高敏感有关。大鼠的母体分离（MS）通过升高 DRN 中的 5-HT 表达导致内脏高敏感。脑室注射内脂素-1 可激活 DRN 5-HT 神经元。在这项研究中，通过对大鼠进行 MS 建立了内脏高敏感模型。采用结肠扩张检测内脏敏感性，通过腹壁回缩反射（AWR）评分和肌电图（EMG）幅度评估。与对照组相比，MS 大鼠的 AWR 评分和 EMG 幅度更高。DRN 中的内脂素-1 和色氨酸羟化酶（TPH，5-HT 合成的限速酶）阳性细胞数量也相应显著升高。与载体处理组相比，DRN 内给予抗内脂素-1/NUCB2 可显著减轻 MS 大鼠的内脏高敏感，同时降低 DRN 中 5-HT 和 TPH 的表达。相反，向正常成年大鼠的 DRN 内给予内脂素-1 会引起内脏高敏感，这与 DRN 中 5-HT 和 TPH 的表达升高有关。总之，内脂素-1 对内脏高敏感有重要影响；其潜在机制可能与 DRN 5-HT 神经元的激活有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/abe022b91bb8/41598_2018_27592_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/04a0e992ed4d/41598_2018_27592_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/a6e448c9975c/41598_2018_27592_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/82032e40a0e1/41598_2018_27592_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/abe022b91bb8/41598_2018_27592_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/04a0e992ed4d/41598_2018_27592_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/1840819bb84e/41598_2018_27592_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/917210c7c2c2/41598_2018_27592_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/3601364fb5c5/41598_2018_27592_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/a6e448c9975c/41598_2018_27592_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/82032e40a0e1/41598_2018_27592_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e3/6008476/abe022b91bb8/41598_2018_27592_Fig7_HTML.jpg

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