Ferrari Merari F R, Reis Eduardo M, Matsumoto João P P, Fior-Chadi Débora R
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, Travessa 14, n.321 Cidade Universitária, Sao Paulo, SP, 05508-090, Brazil.
Cell Mol Neurobiol. 2009 May;29(3):287-308. doi: 10.1007/s10571-008-9321-y. Epub 2008 Oct 24.
The spontaneously hypertensive rat (SHR) is a good model to study several diseases such as the attention-deficit hyperactivity disorder, cardiopulmonary impairment, nephropathy, as well as hypertension, which is a multifactor disease that possibly involves alterations in gene expression in hypertensive relative to normotensive subjects. In this study, we used high-density oligoarrays to compare gene expression profiles in cultured neurons and glia from brainstem of newborn normotensive Wistar Kyoto (WKY) and SHR rats. We found 376 genes differentially expressed between SHR and WKY brainstem cells that preferentially map to 17 metabolic/signaling pathways. Some of the pathways and regulated genes identified herein are obviously related to cardiovascular regulation; in addition there are several genes differentially expressed in SHR not yet associated to hypertension, which may be attributed to other differences between SHR and WKY strains. This constitute a rich resource for the identification and characterization of novel genes associated to phenotypic differences observed in SHR relative to WKY, including hypertension. In conclusion, this study describes for the first time the gene profiling pattern of brainstem cells from SHR and WKY rats, which opens up new possibilities and strategies of investigation and possible therapeutics to hypertension, as well as for the understanding of the brain contribution to phenotypic differences between SHR and WKY rats.
自发性高血压大鼠(SHR)是研究多种疾病的良好模型,如注意力缺陷多动障碍、心肺功能损害、肾病以及高血压,高血压是一种多因素疾病,与正常血压个体相比,高血压患者的基因表达可能发生改变。在本研究中,我们使用高密度寡核苷酸芯片比较了新生正常血压的Wistar Kyoto(WKY)大鼠和SHR大鼠脑干中培养的神经元和神经胶质细胞的基因表达谱。我们发现SHR和WKY脑干细胞之间有376个基因差异表达,这些基因优先映射到17条代谢/信号通路。本文鉴定的一些通路和调控基因明显与心血管调节有关;此外,SHR中有几个差异表达的基因尚未与高血压相关联,这可能归因于SHR和WKY品系之间的其他差异。这为鉴定和表征与SHR相对于WKY所观察到的表型差异(包括高血压)相关的新基因提供了丰富的资源。总之,本研究首次描述了SHR和WKY大鼠脑干细胞的基因谱模式,这为高血压的研究和可能的治疗开辟了新的可能性和策略,也有助于理解大脑对SHR和WKY大鼠表型差异的影响。