Studies on Brain Actions of the Steroid/Growth Factor System

本研究旨在阐明性激素/生长因子系统在围产期脑性分化、神经保护和成熟后神经发生中的作用。通过对我们建立的前颗粒蛋白(PGRN)缺陷小鼠的研究，我们发现PGRN介导雌激素的脑活动，并调节脑性分化、海马齿状回的神经发生和神经退行性变。也有研究表明，PGRN对脑创伤后小胶质细胞的激活具有调节作用。此外，提示PGRN在脑内的作用是通过糖原合成酶-3β的磷酸化，并由含有LIM结构域的基因/蛋白介导的。

This study was conducted to elucidate the role of sex steroid/growth factor systems in sexual differentiation of the brain during perinatal period and neuroprotection as well as neurogenesis after maturation. By the studies using progranulin(PGRN)-deficient mice we have generated, we found that PGRN mediates the brain actions of estrogens and modulates brain sexual differentiation, neurogenesis in the dentate gyrus of the hippocampus and neurodegeneration. It is also demonstrated that PGRN plays a role in regulating the activation of microglia after traumatic brain injury. In addition, it is suggested that the actions of PGRN in the brain is transduced through glycogen synthase kinase 3βphosphorylation, and mediated by genes/proteins containing LIM domain.