Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Clinical and Translational Science Center, Department of Public Health Sciences, Division of Biostatistics, University of California, Davis, CA, United States.
Sci Rep. 2017 Aug 16;7(1):8486. doi: 10.1038/s41598-017-08459-z.
Altered dendritic morphology is common in neurodevelopmental disorders (NDDs), many of which show sex biases in prevalence, onset and/or severity. However, whether dendritic morphology varies as a function of sex in juvenile mice or primary neuronal cell cultures is largely unknown even though both are widely used models for studying NDDs. To address this gap, we quantified dendritic morphology in CA1 pyramidal hippocampal and adjacent somatosensory pyramidal cortical neurons from male and female postnatal day (P)28 C57BL/6J mice. As determined by Sholl analysis of Golgi-stained brain sections, dendritic arbors of male hippocampal neurons are more complex than females. Conversely, dendritic morphology of female cortical neurons is more complex than males. In primary neuron-glia co-cultures from P0 mouse hippocampi, male neurons have more complex dendritic arbors than female neurons. Sex differences are less pronounced in cortical cultures. In vitro sex differences in dendritic morphology are driven in part by estrogen-dependent mechanisms, as evidenced by decreased dendritic complexity in male hippocampal neurons cultured in phenol red-free media or in the presence of an estrogen receptor antagonist. Evidence that sex influences dendritic morphogenesis in two models of neurodevelopment in a region-specific manner has significant mechanistic implications regarding sex biases in NDDs.
树突形态改变在神经发育障碍（NDD）中很常见，其中许多疾病在患病率、发病和/或严重程度上存在性别偏向。然而，即使这两种方法都被广泛用于研究 NDD，幼年小鼠或原代神经元细胞培养物中的树突形态是否会随性别而变化仍知之甚少。为了解决这一差距，我们对来自雄性和雌性出生后第 28 天（P）的 C57BL/6J 小鼠 CA1 海马和相邻体感皮层神经元的树突形态进行了量化。通过对高尔基染色脑切片的 Sholl 分析，确定了雄性海马神经元的树突分支比雌性更为复杂。相反，雌性皮质神经元的树突形态比雄性更为复杂。在来自 P0 小鼠海马的原代神经元-胶质共培养物中，雄性神经元的树突分支比雌性神经元更为复杂。在皮质培养物中，性别差异不那么明显。体外树突形态的性别差异部分是由雌激素依赖性机制驱动的，这表现在用不含酚红的培养基培养或用雌激素受体拮抗剂培养时，雄性海马神经元的树突复杂性降低。这一证据表明，性别以特定区域的方式影响神经发育两种模型中的树突形态发生，这对 NDD 中的性别偏向具有重要的机制意义。
