Swinny Jerome D, Kalicharan Dharamdajal, Brouwer Nieske, Biber Knut, Shi Fuxin, Gramsbergen Albert, van der Want Johannes J L
Laboratory for Cell Biology and Electron Microscopy, University of Groningen, 9713AV Groningen, The Netherlands.
J Comp Neurol. 2004 Apr 19;472(1):40-51. doi: 10.1002/cne.20062.
Urocortin belongs to the family of corticotropin-releasing factor (CRF)-like peptides, which play an important role in sensorimotor coordination. CRF induces locomotor activity, and urocortin has an inhibitory effect. Here, we document the regional and subcellular localization of urocortin in the developing rat cerebellum to compare it with CRF. During the first postnatal week, urocortin immunoreactivity (UCN-ir), within the white matter and cerebellar cortex, was strongest in vermal lobules I, II, IX, and X, closely followed by lobules IV, V, and VIII; lobules VI and VII showed the weakest labeling. Cortical immunoreactivity was in the form of puncta that encircled Purkinje cell somata. By postnatal day (PD) 12, UCN-ir had increased appreciably in all lobules. In Purkinje cells, labeling was spread throughout their somata and proximal dendrites. By PD 15, labeling in lobules I-IV appeared to wane, yet still prevailed in the central and posterior lobules. This anterior-to-posterior gradient persisted through to adulthood. The study shows that urocortin and CRF have similar regional distribution profiles during development, suggesting synergistic roles within the vestibulocerebellum. The onset of the adult distributional pattern of urocortin at the stage when rats are capable of fluent walking patterns further strengthens the correlation between CRF-like peptides and postural control. An important difference between urocortin and CRF is the localization of urocortin, and not CRF, within Purkinje cells, implying that urocortin probably has an additional role in modulating the signals emanating from the cerebellar cortex to the deep cerebellar nuclei.
尿皮质素属于促肾上腺皮质激素释放因子(CRF)样肽家族,这些肽在感觉运动协调中起重要作用。CRF可诱导运动活动,而尿皮质素有抑制作用。在此,我们记录了发育中的大鼠小脑中尿皮质素的区域和亚细胞定位,以便与CRF进行比较。在出生后的第一周,白质和小脑皮质内的尿皮质素免疫反应性(UCN-ir)在蚓部小叶I、II、IX和X中最强,紧随其后的是小叶IV、V和VIII;小叶VI和VII的标记最弱。皮质免疫反应性呈环绕浦肯野细胞胞体的点状。到出生后第12天(PD12),所有小叶中的UCN-ir明显增加。在浦肯野细胞中,标记物遍布其胞体和近端树突。到PD15时,小叶I-IV中的标记似乎减弱,但在中央和后小叶中仍然占主导地位。这种从前到后的梯度一直持续到成年。该研究表明,尿皮质素和CRF在发育过程中具有相似的区域分布模式,提示在前庭小脑中具有协同作用。尿皮质素成年分布模式在大鼠能够流畅行走模式的阶段开始出现,这进一步加强了CRF样肽与姿势控制之间的相关性。尿皮质素和CRF之间的一个重要区别是尿皮质素而非CRF在浦肯野细胞中的定位,这意味着尿皮质素可能在调节从小脑皮质向小脑深部核团发出的信号方面具有额外作用。