Premachandran Hanista, Zhao Mudi, Arruda-Carvalho Maithe
Department of Psychology, University of Toronto Scarborough, Toronto, ON, Canada.
Department of Cell and Systems Biology, University of Toronto Scarborough, Toronto, ON, Canada.
Front Neurosci. 2020 Sep 30;14:583477. doi: 10.3389/fnins.2020.583477. eCollection 2020.
In recent years, a growing body of research has shown sex differences in the prevalence and symptomatology of psychopathologies, such as depression, anxiety, and fear-related disorders, all of which show high incidence rates in early life. This has highlighted the importance of including female subjects in animal studies, as well as delineating sex differences in neural processing across development. Of particular interest is the corticolimbic system, comprising the hippocampus, amygdala, and medial prefrontal cortex. In rodents, these corticolimbic regions undergo dynamic changes in early life, and disruption to their normative development is believed to underlie the age and sex-dependent effects of stress on affective processing. In this review, we consolidate research on sex differences in the hippocampus, amygdala, and medial prefrontal cortex across early development. First, we briefly introduce current principles on sexual differentiation of the rodent brain. We then showcase corticolimbic regional sex differences in volume, morphology, synaptic organization, cell proliferation, microglia, and GABAergic signaling, and explain how these differences are influenced by perinatal and pubertal gonadal hormones. In compiling this research, we outline evidence of and sex differences emerge in the developing corticolimbic system, and illustrate how temporal dynamics of its maturational trajectory may differ in male and female rodents. This will help provide insight into potential neural mechanisms underlying sex-specific critical windows for stress susceptibility and behavioral emergence.
近年来，越来越多的研究表明，在诸如抑郁症、焦虑症以及恐惧相关障碍等精神病理学的患病率和症状学方面存在性别差异，所有这些在生命早期都有很高的发病率。这凸显了在动物研究中纳入雌性受试者的重要性，以及描绘整个发育过程中神经加工的性别差异。特别值得关注的是包含海马体、杏仁核和内侧前额叶皮质的皮质边缘系统。在啮齿动物中，这些皮质边缘区域在生命早期会经历动态变化，其正常发育受到干扰被认为是压力对情感加工产生年龄和性别依赖性影响的基础。在这篇综述中，我们整合了关于早期发育过程中海马体、杏仁核和内侧前额叶皮质性别差异的研究。首先，我们简要介绍当前关于啮齿动物大脑性别分化的原理。然后，我们展示皮质边缘区域在体积、形态、突触组织、细胞增殖、小胶质细胞和γ-氨基丁酸能信号传导方面的性别差异，并解释这些差异是如何受到围产期和青春期性腺激素影响的。在汇编这项研究时，我们概述了发育中的皮质边缘系统中性别差异出现的证据，并说明了其成熟轨迹的时间动态在雄性和雌性啮齿动物中可能如何不同。这将有助于深入了解应激易感性和行为出现的性别特异性关键期潜在的神经机制。
