Understanding the role of steroids in typical and atypical brain development: Advantages of using a "brain in a dish" approach.
Understanding the role of steroids in typical and atypical brain development: Advantages of using a "brain in a dish" approach.
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DOI：
10.1111/jne.12547
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发表时间：
2018-03
影响因子：
3.2
通讯作者：
Srivastava DP
中科院分区：
文献类型：
--
作者：
Adhya D;Annuario E;Lancaster MA;Price J;Baron-Cohen S;Srivastava DP
类固醇在生长、发育、性分化和生殖中具有重要作用。所有四类类固醇，雄激素，雌激素，孕激素和糖皮质激素，对大脑有不同的影响。雄激素和雌激素参与大脑的性别分化，也影响认知。孕激素如孕酮及其代谢产物已被证明参与神经保护，尽管它们的保护作用是时间依赖性的。糖皮质激素与应激和记忆表现有关，也具有剂量和时间依赖性。重要的是，类固醇功能障碍与疾病的发病机制有关。此外，调节类固醇信号传导已被认为是治疗许多神经发育、精神和神经退行性疾病的潜在治疗途径。因此，阐明类固醇在典型和非典型脑功能中的作用对于理解典型脑功能以及确定其在非典型脑中的药理学干预的潜在用途至关重要。然而，迄今为止，大多数研究都是使用动物模型进行的，使用天然人体组织或细胞的工作有限。在这里，我们回顾了类固醇在典型和非典型大脑中的作用，重点是从动物模型确定的这些分子的细胞，分子功能，以及人类研究所强调的治疗潜力。我们进一步讨论了人类诱导多能干细胞的前景，包括在高通量筛选中使用三维神经元培养物（类器官）的优势，加速我们对类固醇在典型大脑中作用的理解，以及它们在理解和治疗非典型大脑中的治疗价值。
Steroids have an important role in growth, development, sexual differentiation and reproduction. All four classes of steroids, androgens, oestrogens, progestogens and glucocorticoids, have varying effects on the brain. Androgens and oestrogens are involved in the sexual differentiation of the brain, and also influence cognition. Progestogens such as progesterone and its metabolites have been shown to be involved in neuroprotection, although their protective effects are timing‐dependent. Glucocorticoids are linked with stress and memory performance, also in a dose‐ and time‐dependent manner. Importantly, dysfunction in steroid function has been implicated in the pathogenesis of disease. Moreover, regulating steroid‐signalling has been suggested as potential therapeutic avenue for the treatment of a number of neurodevelopmental, psychiatric and neurodegenerative disorders. Therefore, clarifying the role of steroids in typical and atypical brain function is essential for understanding typical brain functions, as well as determining their potential use for pharmacological intervention in the atypical brain. However, the majority of studies have thus far have been conducted using animal models, with limited work using native human tissue or cells. Here, we review the effect of steroids in the typical and atypical brain, focusing on the cellular, molecular functions of these molecules determined from animal models, and the therapeutic potential as highlighted by human studies. We further discuss the promise of human‐induced pluripotent stem cells, including advantages of using three‐dimensional neuronal cultures (organoids) in high‐throughput screens, in accelerating our understanding of the role of steroids in the typical brain, and also with respect to their therapeutic value in the understanding and treatment of the atypical brain.
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影响因子：
3.7
作者：
Bramen JE;Hranilovich JA;Dahl RE;Chen J;Rosso C;Forbes EE;Dinov ID;Worthman CM;Sowell ER
通讯作者：
Sowell ER
影响因子：
11
作者：
Brennand, K. J.;Simone, A.;Tran, N.;Gage, F. H.
通讯作者：
Gage, F. H.
影响因子：
2.9
作者：
Allman, John M.;Tetreault, Nicole A.;Park, Soyoung
通讯作者：
Park, Soyoung
影响因子：
3.6
作者：
Casas, Sebastian;Garcia, Sebastian;Yunes, Roberto
通讯作者：
Yunes, Roberto
影响因子：
16.2
作者：
Abud EM;Ramirez RN;Martinez ES;Healy LM;Nguyen CHH;Newman SA;Yeromin AV;Scarfone VM;Marsh SE;Fimbres C;Caraway CA;Fote GM;Madany AM;Agrawal A;Kayed R;Gylys KH;Cahalan MD;Cummings BJ;Antel JP;Mortazavi A;Carson MJ;Poon WW;Blurton-Jones M
通讯作者：
Blurton-Jones M