Yamada Daisuke, Koppensteiner Peter, Odagiri Saori, Eguchi Megumi, Yamaguchi Shun, Yamada Tetsuya, Katagiri Hideki, Wada Keiji, Sekiguchi Masayuki
Department of Degenerative Neurological Diseases, National Center of Neurology and Psychiatry, National Institute of NeuroscienceTokyo, Japan.
Department of Morphological Neuroscience, Graduate School of Medicine, Gifu UniversityGifu, Japan.
Front Neurosci. 2017 Jun 28;11:366. doi: 10.3389/fnins.2017.00366. eCollection 2017.
Information from the peripheral organs is thought to be transmitted to the brain by humoral factors and neurons such as afferent vagal or spinal nerves. The common hepatic branch of the vagus (CHBV) is one of the main vagus nerve branches, and consists of heterogeneous neuronal fibers that innervate multiple peripheral organs such as the bile duct, portal vein, paraganglia, and gastroduodenal tract. Although, previous studies suggested that the CHBV has a pivotal role in transmitting information on the status of the liver to the brain, the details of its central projections remain unknown. The purpose of the present study was to investigate the brain regions activated by the CHBV. For this purpose, we injected L-arginine or anorexia-associated peptide cholecystokinin-8 (CCK), which are known to increase CHBV electrical activity, into the portal vein of transgenic - mice expressing the fluorescent protein Venus under control of the activity-regulated cytoskeleton-associated protein (Arc) promotor. The brain slices were prepared from these mice and the number of Venus positive cells in the slices was counted. After that, c-Fos expression in these slices was analyzed by immunohistochemistry using the avidin-biotin-peroxidase complex method. Intraportal administration of L-arginine increased the number of Venus positive or c-Fos positive cells in the insular cortex. This action of L-arginine was not observed in CHBV-vagotomized mice. In contrast, intraportal administration of CCK did not increase the number of c-Fos positive or Venus positive cells in the insular cortex. Intraportal CCK induced c-Fos expression in the dorsomedial hypothalamus, while intraportal L-arginine did not. This action of CCK was abolished by CHBV vagotomy. Intraportal L-arginine reduced, while intraportal CCK increased, the number of c-Fos positive cells in the nucleus tractus solitarii in a CHBV-dependent manner. The present results suggest that the CHBV can activate different brain regions depending on the nature of the peripheral stimulus.
来自外周器官的信息被认为是通过体液因子和神经元（如传入迷走神经或脊神经）传递到大脑的。迷走神经的肝总分支（CHBV）是主要的迷走神经分支之一，由支配多个外周器官（如胆管、门静脉、副神经节和胃十二指肠 tract）的异质性神经纤维组成。尽管先前的研究表明 CHBV 在将肝脏状态信息传递到大脑中起关键作用，但其向中枢投射的细节仍不清楚。本研究的目的是调查由 CHBV 激活的脑区。为此，我们将已知能增加 CHBV 电活动的 L-精氨酸或厌食相关肽胆囊收缩素-8（CCK）注入在活性调节细胞骨架相关蛋白（Arc）启动子控制下表达荧光蛋白 Venus 的转基因小鼠的门静脉中。从这些小鼠制备脑切片并计数切片中 Venus 阳性细胞的数量。之后，使用抗生物素蛋白-生物素-过氧化物酶复合物法通过免疫组织化学分析这些切片中的 c-Fos 表达。门静脉内注射 L-精氨酸增加了岛叶皮质中 Venus 阳性或 c-Fos 阳性细胞的数量。在 CHBV 切断的小鼠中未观察到 L-精氨酸的这种作用。相反，门静脉内注射 CCK 并未增加岛叶皮质中 c-Fos 阳性或 Venus 阳性细胞的数量。门静脉内 CCK 在背内侧下丘脑诱导 c-Fos 表达，而门静脉内 L-精氨酸则未。CCK 的这种作用被 CHBV 切断所消除。门静脉内 L-精氨酸减少，而门静脉内 CCK 增加，以 CHBV 依赖的方式减少孤束核中 c-Fos 阳性细胞的数量。目前的结果表明，CHBV 可以根据外周刺激的性质激活不同的脑区。
