Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental-CONICET, Buenos Aires, Argentina.
J Neuroendocrinol. 2010 Oct;22(10):1082-92. doi: 10.1111/j.1365-2826.2010.02058.x.
The hippocampus of spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats shows decreased cell proliferation and astrogliosis as well as a reduced number of hilar cells. These defects are corrected after administration of 17β-oestradiol (E(2) ) for 2 weeks. The present work investigated whether E(2) treatment of SHR and of hypertensive DOCA-salt male rats modulated the expression of brain-derived neurotrophic factor (BDNF), a neurotrophin involved in hippocampal neurogenesis. The neurogenic response to E(2) was simultaneously determined by counting the number of doublecortin-immunopositive immature neurones in the subgranular zone of the dentate gyrus. Both hypertensive models showed decreased expression of BDNF mRNA in the granular zone of the dentate gyrus, without changes in CA1 or CA3 pyramidal cell layers, decreased BDNF protein levels in whole hippocampal tissue, low density of doublecortin (DCX)-positive immature neurones in the subgranule zone and decreased length of DCX+ neurites in the dentate gyrus. After s.c. implantation of a single E(2) pellet for 2 weeks, BDNF mRNA in the dentate gyrus, BDNF protein in whole hippocampus, DCX immunopositive cells and the length of DCX+ neurites were significantly raised in both SHR and DOCA-salt-treated rats. These results indicate that: (i) low BDNF expression and deficient neurogenesis distinguished the hippocampus of SHR and DOCA-salt hypertensive rats and (ii) E(2) was able to normalise these biologically important functions in the hippocampus of hypertensive animals.
自发性高血压大鼠（SHR）和去氧皮质酮（DOCA）-盐性高血压大鼠的海马体显示细胞增殖和星形胶质增生减少，以及颗粒下区的齿状回细胞数量减少。这些缺陷在用 17β-雌二醇（E2）治疗 2 周后得到纠正。本研究调查了 E2 治疗 SHR 和高血压 DOCA-盐雄性大鼠是否调节了脑源性神经营养因子（BDNF）的表达，BDNF 是一种参与海马神经发生的神经营养因子。通过计数齿状回颗粒下区双皮质素免疫阳性未成熟神经元的数量，同时确定了 E2 对神经发生的反应。两种高血压模型均显示齿状回颗粒区的 BDNF mRNA 表达减少，而 CA1 或 CA3 锥体细胞层无变化，整个海马组织的 BDNF 蛋白水平降低，颗粒下区双皮质素（DCX）阳性未成熟神经元密度降低，齿状回的 DCX+神经突长度降低。在皮下植入单个 E2 微球 2 周后，SHR 和 DOCA-盐处理大鼠的齿状回 BDNF mRNA、整个海马体的 BDNF 蛋白、DCX 免疫阳性细胞和 DCX+神经突的长度均显著升高。这些结果表明：（i）低 BDNF 表达和神经发生缺陷区分了 SHR 和 DOCA-盐性高血压大鼠的海马体，（ii）E2 能够使高血压动物海马体中的这些重要生物学功能正常化。
