Keyvani Kathy, Sachser Norbert, Witte Otto W, Paulus Werner
Institute of Neuropathology, University Hospital, Muenster, Germany.
J Neuropathol Exp Neurol. 2004 Jun;63(6):598-609. doi: 10.1093/jnen/63.6.598.
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 ipsilesional 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.
丰富的环境可促进受损和未受损大脑的结构变化，并改善行为表现。在两种不同的实验方法中，利用DNA微阵列分析了丰富环境的影响。首先，将饲养在丰富环境中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中的大鼠的相应区域进行比较。其次，诱导影响感觉运动皮层前肢区域的局限性梗死，并分析大鼠非坏死同侧以及对侧同位皮层的基因表达模式（损伤后丰富环境饲养与标准环境饲养）。在未受损的大脑中，海马体有43个上调和15个下调，比感觉运动皮层变化更多，感觉运动皮层有13个上调和4个下调，这表明海马体对环境刺激的反应性更强。在受损大脑中，丰富环境在同侧导致28个下调和14个上调，而在对侧皮层，上调占主导，有46个上调和13个下调。与未受损大脑的类似区域（即感觉运动皮层）相比，对侧皮层中对丰富环境有反应的基因数量更多（59个基因调控），这可能反映了损伤导致的可塑性变化易感性增加。除了损伤周围皮层外，不同脑区/范式中相似的基因功能组受到差异调控，这表明在外部刺激后大脑重组过程中涉及基本相似的分子级联反应。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、迄今未被认识的切入点。
