Pietranera Luciana, Brocca Maria Elvira, Roig Paulina, Lima Analia, Garcia-Segura Luis Miguel, De Nicola Alejandro F
Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina; Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Paraguay 2155, 1425 Buenos Aires, Argentina.
Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina.
J Steroid Biochem Mol Biol. 2015 Feb;146:15-25. doi: 10.1016/j.jsbmb.2014.04.001. Epub 2014 Apr 13.
Estrogens are neuroprotective factors for brain diseases, including hypertensive encephalopathy. In particular, the hippocampus is highly damaged by high blood pressure, with several hippocampus functions being altered in humans and animal models of hypertension. Working with a genetic model of primary hypertension, the spontaneously hypertensive rat (SHR), we have shown that SHR present decreased dentate gyrus neurogenesis, astrogliosis, low expression of brain derived neurotrophic factor (BDNF), decreased number of neurons in the hilus of the dentate gyrus, increased basal levels of the estrogen-synthesizing enzyme aromatase, and atrophic dendritic arbor with low spine density in the CA1 region compared to normotensive Wistar Kyoto (WKY) ratsl. Changes also occur in the hypothalamus of SHR, with increased expression of the hypertensinogenic peptide arginine vasopressin (AVP) and its V1b receptor. Following chronic estradiol treatment, SHR show decreased blood pressure, enhanced hippocampus neurogenesis, decreased the reactive astrogliosis, increased BDNF mRNA and protein expression in the dentate gyrus, increased neuronal number in the hilus of the dentate gyrus, further increased the hyperexpression of aromatase and replaced spine number with remodeling of the dendritic arbor of the CA1 region. We have detected by qPCR the estradiol receptors ERα and ERβ in hippocampus from both SHR and WKY rats, suggesting direct effects of estradiol on brain cells. We hypothesize that a combination of exogenously given estrogens plus those locally synthesized by estradiol-stimulated aromatase may better alleviate the hippocampal and hypothalamic encephalopathy of SHR. This article is part of a Special Issue entitled "Sex steroids and brain disorders".
雌激素是包括高血压脑病在内的脑部疾病的神经保护因子。特别是，海马体在高血压状态下会受到严重损害，在人类高血压患者和动物模型中，海马体的多种功能都会发生改变。通过原发性高血压的遗传模型——自发性高血压大鼠（SHR）开展研究，我们发现，与血压正常的Wistar Kyoto（WKY）大鼠相比，SHR的齿状回神经发生减少、星形胶质细胞增生、脑源性神经营养因子（BDNF）表达降低、齿状回门区神经元数量减少、雌激素合成酶芳香化酶的基础水平升高，并且CA1区树突萎缩、棘突密度降低。SHR的下丘脑也会发生变化，血管紧张素原性肽精氨酸加压素（AVP）及其V1b受体的表达增加。经过长期雌二醇治疗后, SHR的血压降低、海马体神经发生增强、反应性星形胶质细胞增生减少、齿状回中BDNF的mRNA和蛋白表达增加、齿状回门区神经元数量增加、芳香化酶的过表达进一步增加，并且CA1区树突重塑，棘突数量增加。我们通过qPCR检测到SHR和WKY大鼠海马体中均存在雌二醇受体ERα和ERβ，这表明雌二醇对脑细胞有直接作用。我们推测，外源性给予雌激素与雌二醇刺激芳香化酶局部合成的雌激素相结合，可能能更好地缓解SHR的海马体和下丘脑脑病。本文是名为“性类固醇与脑部疾病”的特刊的一部分。
