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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb.
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cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb.

机译:cAMP反应元件结合蛋白调节嗅球中新生神经元的分化和存活。

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摘要

The transcription factor cAMP response element-binding protein (CREB) is involved in multiple aspects of neuronal development and plasticity. Here, we demonstrate that CREB regulates specific phases of adult neurogenesis in the subventricular zone/olfactory bulb (SVZ/OB) system. Combining immunohistochemistry with bromodeoxyuridine treatments, cell tracer injections, cell transplants, and quantitative analyses, we show that although CREB is expressed by the SVZ neuroblasts throughout the neurogenic process, its phosphorylation is transient and parallels neuronal differentiation, increasing during the late phase of tangential migration and decreasing after dendrite elongation and spine formation. In vitro, inhibition of CREB function impairs morphological differentiation of SVZ-derived neuroblasts. Transgenic mice lacking CREB, in a null CREM genetic background, show reduced survival of newborn neurons in the OB. This finding is further supported by peripheral afferent denervation experiments resulting in downregulation of CREB phosphorylation in neuroblasts, the survival of which appears heavily impaired. Together, these findings provide evidence that CREB regulates differentiation and survival of newborn neurons in the OB.
机译:转录因子cAMP反应元件结合蛋白(CREB)参与神经元发育和可塑性的多个方面。在这里,我们证明CREB调节心室下区/嗅球(SVZ / OB)系统中成人神经发生的特定阶段。结合免疫组织化学与溴脱氧尿苷治疗,细胞示踪剂注射,细胞移植和定量分析,我们显示,尽管CREB在整个神经发生过程中均由SVZ神经母细胞表达,但其磷酸化是短暂的并与神经元分化平行,在切向迁移的后期增加并在树突伸长和脊柱形成后减少。在体外,CREB功能的抑制会损害SVZ来源的神经母细胞的形态分化。在无效的CREM遗传背景下,缺少CREB的转基因小鼠在OB中显示出新生神经元的存活率降低。这一发现得到周围传入神经去神经实验的进一步支持,该实验导致神经母细胞中CREB磷酸化的下调,其存活似乎严重受损。在一起,这些发现提供了证据证明CREB调节OB中新生神经元的分化和存活。

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