Sex differences in microRNA expression during development in rat cortex.
Sex differences in microRNA expression during development in rat cortex.
复制标题
DOI：
10.1016/j.neuint.2014.06.007
复制
发表时间：
2014-11
影响因子：
4.2
通讯作者：
Saugstad JA
中科院分区：
文献类型：
--
作者：
Murphy SJ;Lusardi TA;Phillips JI;Saugstad JA
男女之间在患病风险和后果方面存在重要的性别差异。例如，在不同的种族背景和民族中，男性中风的发生频率高于女性。我们实验室和其他人的工作揭示了对脑缺血的性别特异性敏感性，即与女性相比，男性在缺血事件后表现出更大程度的脑损伤。研究表明，男性和女性对缺血易感性的差异可能是由性别之间基因调控和蛋白质表达的先天差异引发的，这些差异与出生后暴露于性激素无关。我们已经证明，在成年男性和女性大脑中的小鼠皮质局灶性脑缺血后，microRNA（miRNA）的表达存在差异。在这里，我们研究的作用，在发展过程中的男性和女性大鼠皮层的差异表达的miRNA作为潜在的效应的表型，导致性别差异缺血。使用TaqMan低密度miRNA阵列和NanoString nCounter分析在从出生后第0天（P0）、出生后第7天（P7）和成年大鼠分离的雄性和雌性皮质中的表达研究揭示了在每个发育阶段雄性和雌性之间的差异miRNA水平。我们重点关注miR-200家族的miRNA，其在P0时在女性中显示出较高的水平，但在P7时在男性中显示出较高的水平，并持续到成年期，并通过单独的qRT-PCR验证了miR-200 a，miR-200 b和miR-429的表达，因为它们聚集在5号染色体上，并且可能是转录共调节的。miR-200 miRNA的预测分析显示，促性腺激素释放激素受体途径中的基因是最重要的靶向基因。这些研究支持miRNA表达的发育变化可能影响成年大脑中的表型，这些表型是对疾病（包括缺血）的性二态反应的基础。
There are important sex differences in the risk and outcome of conditions and diseases between males and females. For example, stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage following an ischemic event compared to females. Studies suggest that the difference in male and female susceptibility to ischemia may be triggered by innate variations in gene regulation and protein expression between the sexes that are independent of post-natal exposure to sex hormones. We have shown that there are differences in microRNA (miRNA) expression in adult male and female brain following focal cerebral ischemia in mouse cortex. Herein we examine a role for differential expression of miRNAs during development in male and female rat cortex as potential effectors of the phenotype that leads to sex differences to ischemia. Expression studies in male and female cortices isolated from postnatal day 0 (P0), postnatal day 7 (P7), and adult rats using TaqMan Low Density MiRNA arrays and NanoString nCounter analysis revealed differential miRNA levels between males and females at each developmental stage. We focused on the miR-200 family of miRNAs that showed higher levels in females at P0, but higher levels in males at P7 that persisted into adulthood, and validated the expression of miR-200a, miR-200b, and miR-429 by individual qRT-PCR as these are clustered on chromosome 5 and may be transcriptionally co-regulated. Prediction analysis of the miR-200 miRNAs revealed that genes within the Gonadotropin Releasing Hormone Receptor pathway are the most heavily targeted. These studies support that developmental changes in miRNA expression may influence phenotypes in adult brain that underlie sexually dimorphic responses to disease, including ischemia.
登录
查看更多内容
影响因子：
3.7
作者：
Brown M;Suryawanshi H;Hafner M;Farazi TA;Tuschl T
通讯作者：
Tuschl T
DOI：
10.1016/j.mrgentox.2010.05.007
发表时间：
2011-06-17
影响因子：
1.9
作者：
Koturbash, Igor;Zemp, Franz;Kovalchuk, Olga
通讯作者：
Kovalchuk, Olga
影响因子：
8.3
作者：
Lee, Soon-Tae;Chu, Kon;Roh, Jae-Kyu
通讯作者：
Roh, Jae-Kyu
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
30.8
作者：
Krek, A;Grun, D;Rajewsky, N
通讯作者：
Rajewsky, N