DNA microarray-based analysis of voluntary resistance wheel running reveals novel transcriptome leading robust hippocampal plasticity.
DNA microarray-based analysis of voluntary resistance wheel running reveals novel transcriptome leading robust hippocampal plasticity.
复制标题
DOI：
10.14814/phy2.12206
复制
发表时间：
2014-11-01
影响因子：
2.5
通讯作者：
Soya H
中科院分区：
文献类型：
--
作者：
Lee MC;Rakwal R;Shibato J;Inoue K;Chang H;Soya H
在两个独立的实验中，用30%体重（RWR）自愿阻力轮跑而不是轮跑（WR）导致更大的增强，包括成年海马神经发生和认知功能，以及海马脑源性神经营养因子（BDNF）信号传导（Lee et al.，J Appl Physiol，2012; Neurosci Lett.，2013年）。在这里，我们的目的是解开新的分子因子，并深入了解RWR增强海马功能的潜在分子机制;高通量全基因组DNA微阵列方法应用于进行4周自愿跑步的大鼠。RWR大鼠的平均跑步距离显着减少，尽管平均工作水平大幅增加，与WR相比增加了约11倍，导致快速收缩跖肌的肌肉适应。全局转录组分析确定了128个（久坐× WR）和169个（久坐× RWR）上调（>1.5倍变化），97个（久坐× WR）和468个（久坐× RWR）下调（<0.75倍变化）基因。使用以途径或特定疾病状态为重点的基因分类和免疫途径分析（IPA）进行的功能分类揭示了疾病和病症、分子功能以及生理系统发育和功能的主要类别中的表达模式变化。RWR特异性调控的基因包括新鉴定的NFATc 1、AVPR 1A和FGFR 4因子，以及先前已知的BDNF和CREB mRNA因子。有趣的是，RWR下调多种炎性细胞因子（IL 1B，IL 2 RA和TNF）和趋化因子（CXCL 1，CXCL 10，CCL 2和CCR 4）与SYCP 3，PRL基因，这可能涉及调节海马神经可塑性变化。这些结果提供了对自愿RWR相关海马转录组的理解，这将为运动积极作用的潜在机制打开一扇窗户，对增强海马功能具有治疗价值。自愿RWR影响大鼠海马转录组的新信息。选择的候选基因可能在RWR海马适应的发展中起关键作用。
In two separate experiments, voluntary resistance wheel running with 30% of body weight (RWR), rather than wheel running (WR), led to greater enhancements, including adult hippocampal neurogenesis and cognitive functions, in conjunction with hippocampal brain‐derived neurotrophic factor (BDNF) signaling (Lee et al., J Appl Physiol, 2012; Neurosci Lett., 2013). Here we aimed to unravel novel molecular factors and gain insight into underlying molecular mechanisms for RWR‐enhanced hippocampal functions; a high‐throughput whole‐genome DNA microarray approach was applied to rats performing voluntary running for 4 weeks. RWR rats showed a significant decrease in average running distances although average work levels increased immensely, by about 11‐fold compared to WR, resulting in muscular adaptation for the fast‐twitch plantaris muscle. Global transcriptome profiling analysis identified 128 (sedentary × WR) and 169 (sedentary × RWR) up‐regulated (>1.5‐fold change), and 97 (sedentary × WR) and 468 (sedentary × RWR) down‐regulated (<0.75‐fold change) genes. Functional categorization using both pathway‐ or specific‐disease‐state‐focused gene classifications and Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions, and physiological system development and function. Genes specifically regulated with RWR include the newly identified factors of NFATc1, AVPR1A, and FGFR4, as well as previously known factors, BDNF and CREB mRNA. Interestingly, RWR down‐regulated multiple inflammatory cytokines (IL1B, IL2RA, and TNF) and chemokines (CXCL1, CXCL10, CCL2, and CCR4) with the SYCP3, PRL genes, which are potentially involved in regulating hippocampal neuroplastic changes. These results provide understanding of the voluntary‐RWR‐related hippocampal transcriptome, which will open a window to the underlying mechanisms of the positive effects of exercise, with therapeutic value for enhancing hippocampal functions. New information on the voluntary RWR influenced transcriptome in rat hippocampus. Selected gene candidates may be a critical role in the development of hippocampal adaptations in RWR.