Haumann Iris, Sturm Muriel Anne, Anstötz Max, Rune Gabriele M
Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
iScience. 2020 May 22;23(5):101077. doi: 10.1016/j.isci.2020.101077. Epub 2020 Apr 18.
In the rodent ventricular-subventricular zone (V-SVZ) neurons are generated throughout life. They migrate along the rostral migratory stream (RMS) into the olfactory bulb before their final differentiation into interneurons and integration into local circuits. Estrogen receptors (ERs) are steroid hormone receptors with important functions in neurogenesis and synaptic plasticity. In this study, we show that the ER GPER1 is expressed in subsets of cells within the V-SVZ of female animals and provide evidence for a potential local estrogen source from aromatase-positive astrocytes surrounding the RMS. Blocking of GPER1 in Matrigel cultures of female animals significantly impairs migration of V-SVZ-derived cells. This outgrowth is accompanied by regulation of phosphorylation of the actin-binding protein cofilin by GPER1 signaling including an involvement of the p21-Ras pathway. Our results point to a prominent role of GPER1 in the initiation of neuronal migration from the V-SVZ to the olfactory bulb.
在啮齿动物的脑室下区（V-SVZ），神经元终生都在产生。它们沿着吻侧迁移流（RMS）迁移到嗅球，然后最终分化为中间神经元并整合到局部神经回路中。雌激素受体（ERs）是类固醇激素受体，在神经发生和突触可塑性中具有重要功能。在本研究中，我们发现ER GPER1在雌性动物V-SVZ内的部分细胞亚群中表达，并为来自RMS周围芳香化酶阳性星形胶质细胞的潜在局部雌激素来源提供了证据。在雌性动物的基质胶培养物中阻断GPER1会显著损害V-SVZ来源细胞的迁移。这种生长伴随着GPER1信号通路对肌动蛋白结合蛋白丝切蛋白磷酸化的调节，包括p21-Ras通路的参与。我们的结果表明，GPER1在神经元从V-SVZ向嗅球迁移的起始过程中起着重要作用。
