Metabolic mapping with cellular resolution: c-fos vs. 2-deoxyglucose.

Metabolic mapping with cellular resolution: c-fos vs. 2-deoxyglucose.
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DOI:
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发表时间:
1993
期刊:
Critical reviews in neurobiology
影响因子:
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通讯作者:
Frank R. Sharp;Stephen M. Sagar;Raymond A. Swanson
Frank R. Sharp;Stephen M. Sagar;Raymond A. Swanson
中科院分区:
其他
文献类型:
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作者:
Frank R. Sharp;Stephen M. Sagar;Raymond A. Swanson

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2-脱氧葡萄糖(2DG)研究在绘制神经系统激活区域图方面最有用。使用2DG的细胞定位研究并没有那么有价值,但结果与目前的观点一致,即突触激活产生的2DG积聚的增加代表主要发生在突触前神经元和可能的神经胶质细胞中的糖酵解葡萄糖代谢的增加。即刻早期基因(IEGs)包括FOS、JUN和NGFI-A家族,由多种细胞内信号通路诱导。这些基因的蛋白质产物的核定位以及它们被各种刺激诱导,使它们在细胞水平上的代谢激活研究中是有用的。渗透、细菌内毒素、类固醇、应激和其他激素刺激;光、听觉、疼痛和其他感官刺激;运动皮质和其他运动行为的刺激;以及作用于包括多巴胺和谷氨酸在内的各种神经递质系统的各种药物和毒素,都可以在神经元中诱导IEGs。此外,c-fos基因表达的定位可以识别体内对生长因子有反应的细胞。视网膜Muller细胞是视网膜的主要胶质细胞类型,在玻璃体内注射表皮生长因子(EGF)或转化生长因子-α(TGF-α)后,可见核Fos免疫染色。这一观察表明,成体胶质细胞可以在体内对这些生长因子做出反应。早期反应基因表达的研究可能特别有助于阐明营养因子在中枢神经系统损伤的细胞反应中的作用。
2-Deoxyglucose (2DG) studies have been most useful in mapping activated regions of the nervous system. Cellular localization studies using 2DG have been less rewarding, but results are consistent with current views that increases of 2DG accumulation produced by synaptic activation represent increases in glycolytic glucose metabolism occurring mainly in presynaptic neuronal and possibly glial elements. Immediate early genes (IEGs), including the fos, jun, and NGFI-A families, are induced by a wide variety of intracellular signaling pathways. The nuclear localization of the protein products of these genes and their induction by a variety of stimuli make them useful in metabolic activation studies carried out at the cellular level. IEGs have been induced in neurons by osmotic, bacterial endotoxin, steroids, stress, and other hormonal stimuli; by light, auditory, painful, and other sensory stimuli; during stimulation of motor cortex and other motor behaviors; and by various drugs and toxins that act on a variety of neurotransmitter systems, including dopamine and glutamate. In addition, the localization of c-fos gene expression identifies cells that respond to growth factors in vivo. Retinal Muller cells, the major glial cell type of the retina, demonstrate nuclear Fos immunostaining after the intravitreal injection of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). This observation demonstrates that adult glia can respond to these growth factors in vivo. The investigation of early response gene expression may be particularly useful for elucidating the role of trophic factors in the cellular response to central nervous system injury.