Kobelt Peter, Paulitsch Stephan, Goebel Miriam, Stengel Andreas, Schmidtmann Marco, van der Voort Ivo R, Tebbe Johannes J, Veh Rüdiger W, Klapp Burghard F, Wiedenmann Bertram, Taché Yvette, Mönnikes Hubert
Department of Medicine, Division Hepatology, Gastroenterology, and Endocrinology, Charité, Campus Virchow, Humboldt-Universität zu Berlin, Germany.
Brain Res. 2006 Oct 30;1117(1):109-17. doi: 10.1016/j.brainres.2006.08.092. Epub 2006 Sep 26.
Peripheral cholecystokinin (CCK) plays a physiological role in the regulation of food intake. The dorsomedial hypothalamic nucleus (DMH) has been implicated in the brain regulation of food intake and satiety. The aim of this study was to determine if peripherally administered CCK affects neuronal activity in the DMH, as assessed by Fos expression. Density of Fos-positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), arcuate nucleus of the hypothalamus (ARC) and ventromedial hypothalamic nucleus (VMH) in non-fasted Sprague-Dawley rats in response to intraperitoneally (ip) injection of CCK-8S (2 microg/kg, n=6) or vehicle (0.15 M NaCl; n=6). CCK-8S increased Fos immunoreactivity in the DMH (mean+/-SEM; cells/section: 108+/-10 versus 54+/-6, p<0.001) and PVN (120+/-12 versus 20+/-3, p<0.001) compared to the vehicle group while not influencing Fos expression in the ARC and VMH. Double labeling showed that 27.4+/-6.4% (n=3) of Fos-positive neurons induced by CCK-8S were positive for corticotropin-releasing factor immunoreactivity, that were mainly localized in the ventral part of the DMH, and encircled in a network of tyrosine-hydroxylase-immunoreactive positive fibers. These data indicate that in addition of the PVN, peripheral CCK increases neuronal activity in the DMH suggesting a possible role in this hypothalamic nucleus in the satiating effect of the peptide.
外周胆囊收缩素（CCK）在食物摄入调节中发挥生理作用。下丘脑背内侧核（DMH）参与了大脑对食物摄入和饱腹感的调节。本研究的目的是确定外周给予的CCK是否会影响DMH中的神经元活动，通过Fos表达进行评估。在未禁食的Sprague-Dawley大鼠中，腹腔注射CCK-8S（2微克/千克，n = 6）或溶剂（0.15 M NaCl；n = 6）后，测定DMH、下丘脑室旁核（PVN）、下丘脑弓状核（ARC）和下丘脑腹内侧核（VMH）中Fos阳性神经元的密度。与溶剂组相比，CCK-8S增加了DMH（平均值±标准误；每切片细胞数：108±10对54±6，p<0.001）和PVN（120±12对20±3，p<0.001）中的Fos免疫反应性，而不影响ARC和VMH中的Fos表达。双重标记显示，CCK-8S诱导的Fos阳性神经元中有27.4±6.4%（n = 3）促肾上腺皮质激素释放因子免疫反应性呈阳性，主要位于DMH的腹侧部分，并被酪氨酸羟化酶免疫反应性阳性纤维网络环绕。这些数据表明，除了PVN外，外周CCK还增加了DMH中的神经元活动，提示该肽在该下丘脑核的饱腹感效应中可能发挥作用。
