Kinnunen A, Lintunen M, Karlstedt K, Fukui H, Panula P
Institute of Biomedicine, Department of Anatomy, University of Helsinki, Finland.
J Comp Neurol. 1998 Apr 27;394(1):127-37.
In the developing brain, histamine is one of the first neurotransmitters to appear. The concentration of histamine in the prenatal brain is fivefold that of adult levels. During the prenatal development a large transiently histamine-immunoreactive cell population distinct from the adult histaminergic system can be found within a subpopulation of the developing serotonergic raphe nuclei neurons. Also histamine-immunoreactive nerve fibers are widely distributed already during the prenatal development extending to the diencephalon, the thalamus, the cortex, and the spinal cord. Large numbers of histamine-containing mast cells also migrate into the brain during the late prenatal life. The wide distribution and high prenatal concentrations imply important functions for the histaminergic system during intrauterine development. However, little is known about the actual functions of histamine during development, and which of the histamine receptors are present in the prenatal rat brain is currently unknown. In the present study, we used in situ hybridization to study the distribution of H1-receptor (H1R) mRNA in the embryonic rat brain and spinal cord. H1R mRNA could be detected in rat brain and in spinal cord on embryonic day (E) 14, and the expression pattern seemed to partially localize in areas containing histamine-immunoreactive nerve fibers through E14-E20. H1R mRNA was also detected by reverse transcriptase polymerase chain reaction from embryonic brain samples and by Northern hybridization. The possible involvement of apoptosis in the disappearance of the developing transiently histaminergic system was studied by using apoptosis detection based on the terminal dUTP nick end labeling (TUNEL) technique and with c-Fos immunostaining. Although histamine immunoreactivity disappears dramatically from the developing raphe nuclei after E18, only occasional apoptotic nuclei could be seen in the histamine-immunoreactive cell bodies. The presence of H1R mRNA during the embryonic development renders it possible that histamine could exert an H1R-specific function at the time of the embryonic histamine peak.
在发育中的大脑中，组胺是最早出现的神经递质之一。产前大脑中组胺的浓度是成人水平的五倍。在产前发育期间，在发育中的血清素能中缝核神经元的一个亚群中，可以发现大量与成组胺能系统不同的、短暂的组胺免疫反应性细胞群体。此外，组胺免疫反应性神经纤维在产前发育期间就已经广泛分布，延伸至间脑、丘脑、皮质和脊髓。大量含组胺的肥大细胞也在产前后期迁移到大脑中。广泛的分布和产前的高浓度意味着组胺能系统在子宫内发育过程中具有重要功能。然而，关于组胺在发育过程中的实际功能知之甚少，目前尚不清楚产前大鼠大脑中存在哪些组胺受体。在本研究中，我们使用原位杂交技术研究了H1受体（H1R）mRNA在胚胎大鼠脑和脊髓中的分布。在胚胎第14天（E14）时，可在大鼠脑和脊髓中检测到H1R mRNA，并且在E14至E20期间，其表达模式似乎部分定位于含有组胺免疫反应性神经纤维的区域。还通过逆转录聚合酶链反应从胚胎脑样本中以及通过Northern杂交检测到了H1R mRNA。通过使用基于末端脱氧尿苷三磷酸缺口末端标记（TUNEL）技术的凋亡检测和c-Fos免疫染色，研究了凋亡在发育中的短暂组胺能系统消失过程中可能的参与情况。尽管在E18后，发育中的中缝核中的组胺免疫反应性急剧消失，但在组胺免疫反应性细胞体中仅偶尔可见凋亡核。胚胎发育期间H1R mRNA的存在使得组胺在胚胎组胺峰值时可能发挥H1R特异性功能成为可能。
