Li Ai-Jun, Wang Qing, Ritter Sue
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman, 99164-6520, USA.
Endocrinology. 2006 Jul;147(7):3428-34. doi: 10.1210/en.2006-0235. Epub 2006 Apr 13.
Hindbrain catecholaminergic neurons are key participants in systemic glucoregulation. However, the specific subpopulations critical for glucoregulatory function have not been fully identified. Here we used in situ hybridization and immunohistochemistry to investigate effects of glucoprivation on expression of the gene for the catecholamine biosynthetic enzyme, dopamine-beta-hydroxylase (DBH), to further localize the critical cell populations. Glucoprivation induced by the glycolytic inhibitor, 2-deoxy-D-glucose (2DG) (250 mg/kg) increased total DBH mRNA expression in caudal ventrolateral medullary cell groups (namely A1, the A1/C1 overlap, and the middle portion of C1) from six to 49 times control levels. In retrofacial C1, no enhancement was observed. In the dorsomedial medulla, hybridization signal was modestly increased (tripled) in A2 but was not increased in the area postrema. Previous microinjection of the retrogradely transported catecholamine immunotoxin (anti-DBH-saporin, or DSAP) into the paraventricular nucleus of the hypothalamus reduced the number of DBH-immunoreactive cells in cell groups known to project to the paraventricular nucleus of the hypothalamus as well as reducing the 2DG-stimulated increases in total DBH mRNA expression in the caudal ventrolateral medulla and A2. The strong enhancement of DBH gene expression by glucoprivation is consistent with the demonstrated importance of catecholaminergic neurons for glucoregulation. The differential sensitivity of these neurons to glucoprivation is evidence of functional specialization within the total population. The pattern of 2DG-induced gene expression indicates that the ventrolateral medulla contains the vast majority of catecholamine neurons responsive to glucoprivation.
后脑儿茶酚胺能神经元是全身葡萄糖调节的关键参与者。然而，对葡萄糖调节功能至关重要的特定亚群尚未完全确定。在这里，我们使用原位杂交和免疫组织化学来研究糖剥夺对儿茶酚胺生物合成酶多巴胺-β-羟化酶（DBH）基因表达的影响，以进一步定位关键细胞群。糖酵解抑制剂2-脱氧-D-葡萄糖（2DG）（250mg/kg）诱导的糖剥夺使尾侧腹外侧髓质细胞群（即A1、A1/C1重叠区和C1中部）的总DBH mRNA表达从对照水平的6倍增加到49倍。在面神经后C1中，未观察到增强。在延髓背内侧，A2区的杂交信号适度增加（增至三倍），但最后区未增加。先前向下丘脑室旁核微量注射逆行转运的儿茶酚胺免疫毒素（抗DBH-皂草素，或DSAP）减少了已知投射到下丘脑室旁核的细胞群中DBH免疫反应性细胞的数量，同时也减少了尾侧腹外侧髓质和A2区中2DG刺激的总DBH mRNA表达的增加。糖剥夺对DBH基因表达的强烈增强与儿茶酚胺能神经元对葡萄糖调节的重要性一致。这些神经元对糖剥夺的不同敏感性证明了整个群体内的功能特化。2DG诱导的基因表达模式表明，腹外侧髓质包含了绝大多数对糖剥夺有反应的儿茶酚胺能神经元。
