Pellegrini-Giampietro D E, Bennett M V, Zukin R S
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
Proc Natl Acad Sci U S A. 1991 May 15;88(10):4157-61. doi: 10.1073/pnas.88.10.4157.
Non-N-methyl-D-aspartate glutamate receptors (GluRs) are encoded by a gene family, known members of which are designated GluR-1, -2, -3, -4, and -5. The present study examined the developmental pattern of GluR-1, -2, and -3 gene expression in rat brain. In situ hybridization revealed different spatial patterns throughout the brain for the cognate mRNAs at all ages examined, as well as different temporal patterns during development. In the adult all three mRNAs were expressed prominently in the pyramidal and granule layers of the hippocampus and in the Purkinje cell layer of the cerebellum, where detailed differences were apparent at the cellular level. In neocortex, GluR-2 mRNA exhibited prominent lamination and regional differences, which were less marked for GluR-1 and -3 mRNAs. In caudate-putamen GluR-2 mRNA was at high levels, but GluR-1 and -3 mRNAs were not. At early ages transcripts were transiently elevated relative to adult levels. GluR-1 mRNA reached peak expression in cortex at postnatal day 14 (P14) (225% of adult), in striatum at P4 (255% of adult), in hippocampus at P14 (195% of adult), and in cerebellum at P21 (150% of adult). GluR-3 exhibited more modest peaks in neocortex and hippocampus. In contrast, GluR-2 mRNA was at near adult levels throughout the first days of postnatal life and exhibited a peak only in cerebellum at P14 (168% of adult). The finding of differential developmental regulation of the GluR-1, -2, and -3 genes indicates that the receptors they encode may have different influences on synaptic plasticity, neuronal survival, and susceptibility to excitatory amino acid toxicity.
非N-甲基-D-天冬氨酸型谷氨酸受体(GluRs)由一个基因家族编码,该家族已知成员被命名为GluR-1、-2、-3、-4和-5。本研究检测了大鼠脑中GluR-1、-2和-3基因表达的发育模式。原位杂交显示,在所检测的所有年龄段,同源mRNA在全脑呈现出不同的空间模式,以及发育过程中的不同时间模式。在成年大鼠中,所有这三种mRNA在海马体的锥体层和颗粒层以及小脑的浦肯野细胞层中均有显著表达,在细胞水平上存在明显的细微差异。在新皮层中,GluR-2 mRNA表现出显著的分层和区域差异,而GluR-1和-3 mRNA的差异则不太明显。在尾状核-壳核中,GluR-2 mRNA水平较高,但GluR-1和-3 mRNA则没有。在早期,转录本相对于成年水平短暂升高。GluR-1 mRNA在出生后第14天(P14)在皮层达到表达峰值(为成年水平的225%),在纹状体中在P4达到峰值(为成年水平的255%),在海马体中在P14达到峰值(为成年水平的195%),在小脑中在P21达到峰值(为成年水平的150%)。GluR-3在新皮层和海马体中表现出较为适度的峰值。相比之下,GluR-2 mRNA在出生后的头几天一直处于接近成年水平,仅在P14时在小脑中出现峰值(为成年水平的168%)。GluR-1、-2和-3基因发育调控差异的发现表明,它们所编码的受体可能对突触可塑性、神经元存活以及对兴奋性氨基酸毒性的易感性具有不同的影响。