Bahn S, Volk B, Wisden W
MRC Laboratory of Molecular Biology, Neurobiology Division, Cambridge, United Kingdom.
J Neurosci. 1994 Sep;14(9):5525-47. doi: 10.1523/JNEUROSCI.14-09-05525.1994.
Kainate-preferring receptors are a subclass of ionotropic glutamate receptors that might play a role in brain development. The expression of the five known genes encoding kainate receptor subunits (GluR-5, -6, -7, KA-1, and KA-2) was studied by in situ hybridization during pre- and postnatal development of the rat brain. We compared the combined expression patterns of these genes with autoradiography using 3H-kainate in the developing brain from embryonic day 12 (E12) through to adult. Although mRNAs for the receptor subunits (except KA-1) can be detected at stage E12, 3H-kainic acid binding (as an index of receptor protein) is not found at this stage. However, by E14 high-affinity kainate sites are found throughout the gray matter, but particularly in spinal cord, primordial cerebellum, and ventral forebrain structures. All genes undergo a peak in their expression in the late embryonic/early postnatal period. GluR-5 expression during development shows the most interesting features because the changes are qualitative. The GluR-5 gene shows peaks of expression around the period of birth in the sensory cortex (layers II, III, and IV), in CA1 hippocampal interneurons in the stratum oriens, in the septum, and in the thalamus. GluR-6 shows a prenatal expression peak in the cingulate gyrus of the neocortex. KA-1 transcripts appear with the development of the hippocampus and remain largely confined to discrete areas such as the CA3 region, the dentate gyrus, and subiculum. KA-2 transcripts are found throughout the CNS from as early as E12 and remain constant until adulthood. The GluR-5 and GluR-6 genes are coexpressed in multiple peripheral ganglia (e.g., cranial nerve ganglia, dorsal root ganglia, and mural ganglia) at E14.
红藻氨酸受体是离子型谷氨酸受体的一个亚类,可能在大脑发育中发挥作用。我们通过原位杂交技术研究了在大鼠脑产前和产后发育过程中,编码红藻氨酸受体亚基(GluR - 5、- 6、- 7、KA - 1和KA - 2)的五个已知基因的表达情况。我们将这些基因的联合表达模式与从胚胎第12天(E12)到成年期发育中的大脑中使用³H - 红藻氨酸进行的放射自显影进行了比较。尽管在E12阶段可以检测到受体亚基(KA - 1除外)的mRNA,但在此阶段未发现³H - 红藻氨酸结合(作为受体蛋白的指标)。然而,到E14时,在整个灰质中发现了高亲和力的红藻氨酸位点,尤其是在脊髓、原始小脑和腹侧前脑结构中。所有基因在胚胎后期/出生后早期表达均达到峰值。发育过程中GluR - 5的表达表现出最有趣的特征,因为其变化是定性的。GluR - 5基因在感觉皮层(II、III和IV层)、海马体CA1区的海马中间神经元、隔区和丘脑出生前后的时期表达达到峰值。GluR - 6在新皮质扣带回中表现出产前表达峰值。KA - 1转录本随着海马体的发育而出现,并且在很大程度上局限于离散区域,如CA3区、齿状回和下托。早在E12时,KA - 2转录本就在整个中枢神经系统中被发现,并一直保持到成年期。在E14时,GluR - 5和GluR - 6基因在多个外周神经节(如脑神经节、背根神经节和壁神经节)中共同表达。