King James S, Bishop Georgia A
Department of Neuroscience, The Ohio State University, 333 W. 10th Ave. Columbus, Ohio 43210, USA.
J Neurocytol. 2003 Mar;32(3):305-16. doi: 10.1023/B:NEUR.0000010088.99394.db.
Corticotropin releasing factor (CRF) is present in the adult, as well as in the embryonic and postnatal rodent cerebellum. Further, the distribution of the type 1 CRF receptor has been described in adult and postnatal animals. The focus of the present study is to determine the distribution and cellular relationships of the type 1 CRF receptor (CRF-R1) during embryonic development of the cerebellum. Between embryonic day (E)11 and E12, CRF-R1 immunoreactive puncta are uniformly distributed in the ventricular zone, the site of origin of Purkinje cells, nuclear neurons, and GABAergic interneurons, as well as the germinal trigone, the birthplace of the precursors of granule cells. Between E13 and 18, the distribution of immunolabeled puncta decreases in both the ventricular zone and the germinal trigone and increases in the intermediate zone, as well as in the dorsal aspect of the cerebellar plate. Between E14 and 18, antibodies that label specific populations of cerebellar neurons were combined with the antibody for the receptor to determine the cellular elements that expressed CRF-R1. At E14, CRF-R1 immunoreactivity is co-localized in neurons immunolabeled with PAX-2, an antibody that is specific for GABAergic interneurons. These neurons continue to express CRF-R1 as they migrate dorsally toward the cerebellar surface. Between E16 and 18, Purkinje cells, immunolabeled with calbindin, near the dorsal surface of the cerebellum express CRF-R1 in their cell bodies and apical processes. CRF has been shown to have a depolarizing effect on adult and postnatal Purkinje cells. Further, CRF has been shown to contribute to excitability of hippocampal neurons during embryonic development by binding to CRF-R1; depolarization induced excitability appears to be critical for cell survival. The location of the type one CRF receptor and the presence of its primary ligand, CRF, in the germinal zones of the cerebellum and in migrating neurons suggest that this receptor/ligand interaction could be important in the regulation of neuronal survival through cellular mechanisms that lead to depolarization of embryonic cerebellar neurons.
促肾上腺皮质激素释放因子（CRF）存在于成年啮齿动物的小脑以及胚胎期和出生后的啮齿动物小脑中。此外，1型CRF受体在成年和出生后动物中的分布已有描述。本研究的重点是确定小脑胚胎发育过程中1型CRF受体（CRF-R1）的分布及其细胞关系。在胚胎第（E）11天和E12天之间，CRF-R1免疫反应性斑点均匀分布于室管膜区，即浦肯野细胞、核神经元和GABA能中间神经元的起源部位，以及生发三角区，即颗粒细胞前体的诞生地。在E13至18天之间，免疫标记斑点在室管膜区和生发三角区的分布减少，而在中间区以及小脑板背侧增加。在E14至18天之间，将标记小脑神经元特定群体的抗体与该受体的抗体相结合，以确定表达CRF-R1的细胞成分。在E14天，CRF-R1免疫反应性与用PAX-2免疫标记的神经元共定位，PAX-2是一种对GABA能中间神经元特异的抗体。这些神经元在向小脑表面背侧迁移时继续表达CRF-R1。在E16至18天之间，在小脑背侧表面附近用钙结合蛋白免疫标记的浦肯野细胞在其细胞体和顶端突起中表达CRF-R1。已证明CRF对成年和出生后的浦肯野细胞有去极化作用。此外，已证明CRF在胚胎发育过程中通过与CRF-R1结合促进海马神经元的兴奋性；去极化诱导的兴奋性似乎对细胞存活至关重要。小脑生发区和迁移神经元中1型CRF受体的定位及其主要配体CRF的存在表明，这种受体/配体相互作用可能通过导致胚胎小脑神经元去极化的细胞机制在神经元存活调节中起重要作用。
