Inagaki S, Kubota Y, Shimada S, Tohyama M, Kito S, MacIntyre I, Takagi H
First Department of Anatomy, Osaka City University Medical School, Japan.
Brain Res. 1988 Oct 1;471(2):235-48. doi: 10.1016/0165-3806(88)90102-2.
Ontogeny of the calcitonin gene-related peptide (CGRP)-containing structures was investigated in the forebrain and diencephalon of the rat by means of indirect immunofluorescence. CGRP-like immunoreactive (CGRP-IR) fibers first appeared at gestational day 18 (E18) in the primordia of the bed nucleus of the stria terminalis, central amygdaloid nucleus and posterolateral portion of the lateral hypothalamic nucleus. CGRP-IR fibers gradually increased in immunoreactivity and in number in these nuclei toward birth. A pronounced increase of CGRP-like immunoreactive fibers was found after birth in these nuclei and made very dense plexuses of fibers in adult animals. A few CGRP-IR fibers first appeared at the perinatal stage in the lateral septum, the most caudal portion of the caudate-putamen, and ventromedial and ventroposterior thalamic nuclei. Then the immunoreactive fibers increased and dense plexuses were present in these brain areas of the adult. A small number of immunoreactive fibers appeared at postnatal day 4-7 (P4-7) in the caudal insular cortex and ventromedial hypothalamic nucleus. A significant number of fibers was present in these areas of the adult. On the other hand, CGRP-like immunoreactivity in cell bodies was first detected with faint immunofluorescence at P4 in the anteromedial parts of the lateral hypothalamic area and ventromedial and ventroposterior thalamic nuclei. Thereafter CGRP-IR cells increased in immunoreactivity, and a significant number of cells was noted in these nuclei of the adult. In addition, CGRP-IR cells are identified in the medial amygdaloid nucleus, and medial preoptic area at P14. In conclusion, in the forebrain and diencephalon (1) CGRP-like immunoreactivity appears in fibers earlier than in cell bodies, suggesting that at least some of immunoreactive fibers originate from the lower brainstem, and (2) high density of CGRP-IR structures present in the brain at embryonic and early postnatal stages may indicate that CGRP could be an important factor involved in the developmental organization of the central nervous system.
通过间接免疫荧光法，研究了大鼠前脑和间脑中含降钙素基因相关肽（CGRP）结构的个体发生。CGRP样免疫反应性（CGRP-IR）纤维首先在妊娠第18天（E18）出现在终纹床核、中央杏仁核和下丘脑外侧核后外侧部分的原基中。这些核中CGRP-IR纤维的免疫反应性和数量在出生前逐渐增加。出生后，这些核中CGRP样免疫反应性纤维显著增加，并在成年动物中形成非常密集的纤维丛。少数CGRP-IR纤维在围产期首先出现在外侧隔、尾壳核最尾端部分以及丘脑腹内侧核和腹后核。然后，免疫反应性纤维增加，并在成年动物的这些脑区中形成密集的纤维丛。少数免疫反应性纤维在出生后第4-7天（P4-7）出现在尾侧岛叶皮质和下丘脑腹内侧核。成年动物的这些区域中有大量纤维。另一方面，在出生后第4天，在下丘脑外侧区的前内侧部分以及丘脑腹内侧核和腹后核中，首次通过微弱的免疫荧光检测到细胞体中的CGRP样免疫反应性。此后，CGRP-IR细胞的免疫反应性增加，并且在成年动物的这些核中有大量细胞被观察到。此外，在出生后第14天，在内侧杏仁核和内侧视前区中鉴定出CGRP-IR细胞。总之，在前脑和间脑中，（1）CGRP样免疫反应性在纤维中比在细胞体中出现得更早，这表明至少一些免疫反应性纤维起源于低位脑干，并且（2）在胚胎期和出生后早期阶段，脑中存在的高密度CGRP-IR结构可能表明CGRP可能是参与中枢神经系统发育组织的一个重要因素。
