Localization and characterization of pituitary adenylate cyclase-activating polypeptide receptors in the human cerebellum during development
Localization and characterization of pituitary adenylate cyclase-activating polypeptide receptors in the human cerebellum during development
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DOI：
10.1002/cne.20934
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发表时间：
2006-06-01
影响因子：
2.5
通讯作者：
Gonzalez, B
中科院分区：
文献类型：
--
作者：
Basille, M;Cartier, D;Gonzalez, B
腺苷酸环化酶激活多肽（PACAP）受体在啮齿类动物小脑皮质层中表达活跃，并参与小脑发育。本报告提供了第一个解剖定位和PACAP受体在发育中的人小脑的特点。从15周龄胎儿到22岁受试者的RT-PCR分析表明，PAC 1-R和VPAC 1-R在小脑的所有阶段都有表达，而VPAC 2-R mRNA几乎检测不到。原位杂交标记表明，在人类胎儿中，PAC 1-R mRNA与外部颗粒细胞层（EGL），一个发芽的神经上皮细胞，并与内部颗粒细胞层（IGL）。VPAC 1-R mRNA的分布模式与PAC 1-R mRNA的分布模式非常相似，而VPAC 2-R mRNA仅在7-22岁的受试者中可见。[I-125] PACAP 27结合位点的定位与PAC 1-R和VPAC 1-R mRNA的分布完全一致。药理学表征显示，在15-24周龄胎儿的EGL和IGL以及7-22岁患者的颗粒细胞层中，结合位点表现出PAC 1-R特征。相反，在成人小脑的分子层和髓质中观察到的PACAP结合位点由PAC 1-R和VPAC（1/2）-R的异质群体组成。总之，这些数据提供了PACAP受体在人类小脑皮质中表达的第一个证据。PAC 1-R是在胎儿中发现的主要PACAP受体，并且PAC 1-R和VPAC 1-R都在成熟小脑中表达。这些结果表明，PACAP在人类小脑中具有神经发育功能。
Pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are actively expressed in the cortical layers of the cerebellum of rodents and contribute to cerebellar development. The present report provides the first anatomical localization and characterization of PACAP receptors in the developing human cerebellum. RT-PCR analysis from 15-week-old fetuses to 22-year-old subject showed that PAC1-R and VPAC1-R are expressed in the cerebellum at all stages, whereas VPAC2-R mRNA was barely detectable. In situ hybridization labeling indicated that, in human fetuses, PAC1-R mRNA is associated with the external granule cell layer (EGL), a germinative neuroepithelium, and with the internal granule cell layer (IGL). The distribution pattern of VPAC1-R mRNA was very similar to that of PAC1-R mRNA, whereas VPAC2-R mRNA was visualized only in 7-22-year-old subjects. The localization of [I-125]PACAP27 binding sites was fully consistent with the distribution of PAC1-R and VPAC1-R mRNA. Pharmacological characterization revealed that, in the EGL and IGL from 15-24-week-old fetuses and in the granule cell layer from 7-22-year-old patients, binding sites exhibit a PAC1-R profile. In contrast, PACAP binding sites observed in the molecular layer and medulla of the adult cerebellum consisted of a heterogeneous population of PAC1-R and VPAC(1/2)-R. Altogether, these data provide the first evidence that PACAP receptors are expressed in the human cerebellar cortex. PAC1-R is the predominant PACAP receptor found in fetuses, and both PAC1-R and VPAC1-R are expressed in the mature cerebellum. These observations suggest that PACAP has neurodevelopmental functions in the human cerebellum.