SYNAPTIC ACTIVATION OF NF-KAPPA-B BY GLUTAMATE IN CEREBELLAR GRANULE NEURONS IN-VITRO
SYNAPTIC ACTIVATION OF NF-KAPPA-B BY GLUTAMATE IN CEREBELLAR GRANULE NEURONS IN-VITRO
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DOI：
10.1073/pnas.92.20.9077
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发表时间：
1995-09-26
影响因子：
11.1
通讯作者：
DENISDONINI, S
中科院分区：
文献类型：
--
作者：
GUERRINI, L;BLASI, F;DENISDONINI, S
神经元的增殖、迁移和分化是由特定基因在特定发育阶段的顺序表达调控的。这些过程依赖于通过第二信使系统调节的差异基因表达，出生后早期小鼠小脑颗粒细胞迁移到内部颗粒层并获得分化特性。神经递质谷氨酸已被证明在这一发育过程中起重要作用，我们在这里通过免疫组织化学发现转录因子NP-kappa B的RelA亚基存在；在老鼠大脑的几个区域。此外，免疫荧光显微镜和电泳迁移试验表明，在3至7日龄小鼠的小脑颗粒细胞培养中，谷氨酸特异性地激活转录因子NF-kappa B，如核提取物蛋白结合到合成的寡核苷酸上，可复制人类免疫缺陷病毒的kappa B位点。不同谷氨酸受体拮抗剂的使用表明，谷氨酸的作用主要通过n -甲基- d -天冬氨酸（NMDA）受体激活发生，可能是由于细胞内Ca2+的增加。突触的特异性效应强烈建议的观察谷氨酸未能激活nf -κB在星形胶质细胞,而细胞因子,如白介素1α和肿瘤坏死因子α,这样做时,谷氨酸的影响似乎发育监管,实际上,nf -κB中发现一种诱导的神经元的胞浆3 - 7-day-old老鼠但持续激活核的神经元来自老崽(产后8 - 10天)。总之，这些观察结果表明存在一种跨突触调控基因表达的新途径。
Neuronal proliferation, migration, and differentiation are regulated by the sequential expression of particular genes at specific stages of development. Such processes rely on differential gene expression modulated through second-messenger systems, Early postnatal mouse cerebellar granule cells migrate into the internal granular layer and acquire differentiated properties. The neurotransmitter glutamate has been shown to play an important role in this developmental process, We show here by immunohistochemistry that the RelA subunit of the transcription factor NP-kappa B is present;in several areas of the mouse brain. More over, immunofluorescence microscopy and electrophoretic mobility-shift assay demonstrate that in cerebellar granule cell cultures derived from 3- to 7-day-old mice, glutamate specifically activates the transcription factor NF-kappa B, as shown by binding of nuclear extract proteins to a synthetic oligonucleotide reproducing the kappa B site Of human immunodeficiency virus, The use of different antagonists of the glutamate receptors indicates that the effect of glutamate occurs mainly via N-methyl-D-aspartate (NMDA)-receptor activation, possibly as a result of an increase in intracellular Ca2+. The synaptic specificity of the effect is strongly suggested by the observation that glutamate failed to activate NF-kappa B in astrocytes, while cytokines, such as interleukin 1 alpha and tumor necrosis factor alpha, did so, The effect of glutamate appears to be developmentally regulated, Indeed, NF-kappa B is found in an inducible form in the cytoplasm of neurons of 3- to 7-day-old mice but is constitutively activated in the nuclei of neurons derived from older pups (8-10 days postnatal). Overall, these observations suggest the existence of a new pathway of transynaptic regulation of gene expression.