Gene expression profiling in the intact and injured brain following environmental enrichment

Gene expression profiling in the intact and injured brain following environmental enrichment
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DOI:
10.1093/jnen/63.6.598
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发表时间:
2004-06-01
影响因子:
3.2
通讯作者:
Paulus, W
Paulus, W
中科院分区:
医学4区
文献类型:
--
作者:
Keyvani, K;Sachser, N;Paulus, W

文献摘要

被引文献

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丰富的环境可以促进受伤和完整大脑的结构变化,并改善行为表现。在两种不同的实验方法中,利用 DNA 微阵列分析了富集环境的影响。首先,将具有丰富外壳的未受伤成年大鼠的感觉运动皮层和海马体的基因表达模式与饲养在标准笼子中的大鼠的类似区域进行比较。其次,诱导影响感觉运动皮层前肢区域的局限性梗塞,并分析大鼠非坏死同位皮层和对侧同位皮层(病灶后富集外壳与标准外壳)的基因表达模式。在完整的大脑中,海马体(有 43 个上调和 15 个下调)比感觉运动皮层(有 13 个上调和 4 个下调)显示出更多的变化,表明海马体对环境刺激的反应性更强。在受伤的大脑中,富集导致对侧皮质有 28 种下调和 14 种上调,而在对侧皮质中,上调占主导地位,有 46 种上调和 13 种下调。与完整大脑的类似区域(即感觉运动皮层)(17 个基因调节)相比,对侧皮层(59 个基因调节)中的富集响应的基因数量较多,可能反映了由于损伤而导致的塑性变化的敏感性增加。除病灶周围皮质外,相似的基因功能组在不同的大脑区域/范式中受到差异性调节。这表明在外部刺激后大脑的重组过程中涉及基本相似的分子级联。这里检测到的许多基因对应于已知参与神经可塑性的分子途径,而其他基因则提供了新的且迄今为止未被识别的切入点。
An enriched environment promotes structural changes in both injured and intact brain and improves behavioral performance. In 2 different experimental approaches, the effects of enriched surroundings were analyzed utilizing DNA microarrays. First, gene expression patterns of the sensorimotor cortex and the hippocampus of noninjured adult rats with enriched housing were compared with analogous regions of rats kept in standard cages. Second, circumscribed infarcts affecting the forelimb area of the sensorimotor cortex were induced, and gene expression patterns of the non-necrotic ipsi-lesional as well as the contralesional homotopic cortex of rats (postlesionally enriched housing versus standard) were analyzed. In the intact brain, the hippocampus, which had 43 upregulations and 15 downregulations showed more changes than the sensorimotor cortex, which had 13 upregulations and 4 downregulations, indicating a greater responsiveness of the hippocampus to environmental stimuli. In the injured brain, enrichment led ipsilesionally to 28 downregulations and 14 upregulations, while in the contralesional cortex, upregulations prevailed with 46 upregulations and 13 downregulations. The larger number of genes responsive to enrichment in the contralesional cortex (59 gene regulations) as compared to the analogous area (i.e. sensorimotor cortex) of the intact brain (17 gene regulations) likely reflects increased susceptibility for plastic changes due to injury. With the exception of the perilesional cortex, similar functional groups of genes were differentially regulated in different brain regions/paradigms. suggesting basically similar molecular cascades being involved in reorganizing the brain following external stimuli. Many of the genes detected here correspond to molecular pathways known to be involved in neuroplasticity, whereas others provide new and hitherto unrecognized entry points.