Université d'Aix-Marseille I - Laboratoire de Neurobiologie Intégrative et Adaptative - UMR/CNRS 6149 - Pôle 3C - 3 Place Victor Hugo, 13331 Marseille Cedex 03, France.
Neurobiol Aging. 2011 Mar;32(3):470-85. doi: 10.1016/j.neurobiolaging.2009.03.010. Epub 2009 Apr 23.
The aim of this study was to determine the neurobiological bases of behavioral deficits associated with cholinergic damage and the potential of long-term environmental enrichment as a therapeutic agent. Rats were submitted to intra-structures injection of 192 IgG-saporin and then behaviorally tested 1 month and 1 year post-lesion in a nonmatching-to-position task. The gene expression changes were assessed by cDNA macroarray technology using the GE array Q series designed to profile the expression of neurotrophic signaling molecules. Results showed that (1) cholinergic injury modulated the expression of genes such as brain-derived neurotrophin factor but also genes associated with inflammatory response, neuron apoptosis, regulation of angiogenesis, and synaptic plasticity, (2) aging is associated with regulation of glial proliferation and apoptosis, and (3) long-term enriched environment housing enhanced behavioral performance in lesioned and non-lesioned rats and upregulated gene expression. This therapeutic role of the enriched environment seemed to be associated with a suppression of expression of genes involved in apoptosis, glial cell differentiation, and cell cycle, but also with an enhanced expression of a subset of genes involved in signal transduction.
本研究旨在确定与胆碱能损伤相关的行为缺陷的神经生物学基础，以及长期环境丰富作为治疗剂的潜力。大鼠接受 192 IgG-saporin 结构内注射，然后在损伤后 1 个月和 1 年内进行非位置匹配任务的行为测试。使用设计用于分析神经营养信号分子表达的 GE 阵列 Q 系列的 cDNA 宏阵列技术评估基因表达变化。结果表明：（1）胆碱能损伤调节了脑源性神经营养因子等基因的表达，也调节了与炎症反应、神经元凋亡、血管生成调节和突触可塑性相关的基因；（2）衰老与胶质细胞增殖和凋亡的调节有关；（3）长期丰富环境饲养增强了损伤和未损伤大鼠的行为表现，并上调了基因表达。这种丰富环境的治疗作用似乎与凋亡、神经胶质细胞分化和细胞周期相关基因表达的抑制有关，但也与参与信号转导的一组基因的增强表达有关。
