Zhang Weizhen, Hu Yuexuan, Lin Theodore R, Fan Yongyi, Mulholland Michael W
Michigan Gastrointestinal Peptide Center, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Peptides. 2005 Nov;26(11):2280-8. doi: 10.1016/j.peptides.2005.04.023. Epub 2005 Jul 6.
Ghrelin, a gastric hormone, regulates growth hormone secretion and energy homeostasis. The present study shows that ghrelin promotes neural proliferation in vivo and in vitro in the rat nucleus of the solitary tract (NTS). Systemic administration of ghrelin significantly increased 5-bromo-2'-deoxyuridine (BrdU) incorporation in the NTS in adult rats with cervical vagotomy. Cultured NTS neurons contain immature precursor cells as shown by expression of Hu protein. Exposure of cultured NTS neurons to ghrelin significantly increased the percentage of BrdU incorporation into cells in both dose- and time-dependent manners. Co-localization of Hu immunoreactivity with BrdU labeling was demonstrated by double fluorescent staining, suggesting that cells labeled with BrdU are neuronal cells. Ghrelin receptor mRNA was detected in tissues from the NTS. The mitotic effect of ghrelin was abolished by treatment of cultured NTS neurons with ghrelin receptor antagonists: D-Lys-3-GHRP-6 and [D-Arg1, D-Phe-5, D-Trp-7, 9, Leu-11] substance P. Diltiazem, a L-type calcium channel blocker, significantly attenuated ghrelin-mediated increments in BrdU incorporation. Ghrelin acts directly on NTS neurons to stimulate neurogenesis.
胃饥饿素是一种胃激素，可调节生长激素分泌和能量平衡。本研究表明，胃饥饿素在体内和体外均可促进大鼠孤束核（NTS）的神经增殖。对成年大鼠进行颈迷走神经切断术后，全身注射胃饥饿素可显著增加NTS中5-溴-2'-脱氧尿苷（BrdU）的掺入量。培养的NTS神经元含有未成熟的前体细胞，如Hu蛋白的表达所示。将培养的NTS神经元暴露于胃饥饿素中，可显著增加BrdU掺入细胞的百分比，且呈剂量和时间依赖性。通过双重荧光染色证明了Hu免疫反应性与BrdU标记的共定位，表明用BrdU标记的细胞是神经元细胞。在NTS组织中检测到胃饥饿素受体mRNA。用胃饥饿素受体拮抗剂：D-赖氨酸-3-GHRP-6和[D-精氨酸1，D-苯丙氨酸5，D-色氨酸7，9，亮氨酸11]P物质处理培养的NTS神经元后，胃饥饿素的有丝分裂作用被消除。L型钙通道阻滞剂地尔硫卓可显著减弱胃饥饿素介导的BrdU掺入增加。胃饥饿素直接作用于NTS神经元以刺激神经发生。
