Nuñez J L, McCarthy M M
Department of Physiology, Program in Neuroscience, University of Maryland, 655 W Baltimore Street, Baltimore, MD 21201, USA.
Neuroscience. 2009 Jan 23;158(2):623-34. doi: 10.1016/j.neuroscience.2008.09.061. Epub 2008 Nov 1.
The maturation of the hippocampus is impacted by a multitude of factors, including the regulation of intracellular calcium levels. Depolarizing actions of Gamma-Aminobutyric Acid (GABA) can profoundly alter intracellular calcium in immature hippocampal neurons via influx through voltage-gated calcium channels. We here report fundamental sex differences in properties of depolarizing GABA responses and in resting intracellular calcium in neonatal cultured hippocampal neurons. The effects of the estrogen receptor antagonist, ICI 182,780, and the estradiol-synthesis inhibitor, formestane, indicate the sex differences in depolarizing GABA responses are at least in part due to de novo estradiol synthesis by female neurons, whereas a sex difference in resting calcium is independent of steroids. We postulate that local estradiol synthesis in cultured female hippocampal neurons affects the kinetics of either the GABA(A) receptor or voltage sensitive calcium channels. These data highlight the fact that immature hippocampal neurons exhibit fundamentally different physiological properties in males versus females. Elucidating how and where immature male and female neurons differ is essential for a complete understanding of normal rodent brain development.
海马体的成熟受到多种因素的影响，包括细胞内钙水平的调节。γ-氨基丁酸（GABA）的去极化作用可通过电压门控钙通道内流，深刻改变未成熟海马神经元的细胞内钙。我们在此报告了新生培养海马神经元中去极化GABA反应特性和静息细胞内钙的基本性别差异。雌激素受体拮抗剂ICI 182,780和雌二醇合成抑制剂福美司坦的作用表明，去极化GABA反应的性别差异至少部分归因于雌性神经元从头合成雌二醇，而静息钙的性别差异与类固醇无关。我们推测，培养的雌性海马神经元中局部雌二醇合成会影响GABA(A)受体或电压敏感钙通道的动力学。这些数据突出了一个事实，即未成熟海马神经元在雄性和雌性中表现出根本不同的生理特性。阐明未成熟雄性和雌性神经元在哪些方面以及如何不同，对于全面理解正常啮齿动物大脑发育至关重要。
