2024年8月22日，《细胞》杂志在线发表了美国哈佛医学院Bernardo L. Sabatini团队的最新成果。该研究发现，甲状腺激素重塑皮层以协调全身代谢和探索行为。
研究人员发现甲状腺激素（一种在许多外周器官中调节代谢的因子）直接激活成年雄性小鼠前额叶皮层中特定细胞类型的转录程序。这些程序在谷氨酸能投射神经元中富含轴突引导基因，在星形胶质细胞和神经元中富含突触调节基因，并在少突胶质细胞中富含促髓鞘形成因子，这表明皮层回路具有广泛的可塑性。
实际上，全细胞电生理学揭示甲状腺激素改变了兴奋性和抑制性突触传递，这一效应需要甲状腺激素诱导的突触前神经元基因调控程序。此外，甲状腺激素在前额叶皮层的作用调节了先天的探索行为，并因果地促进了探索决策。因此，甲状腺激素直接作用于雄性大脑皮层，以协调探索行为与全身代谢状态。
据介绍，动物通过改变内部器官的功能（包括大脑）来适应环境条件。为了实现适应，行为的变化必须与全身器官的功能状态协调。
附：英文原文
Title: Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration
Author: Daniel R. Hochbaum, Lauren Hulshof, Amanda Urke, Wengang Wang, Alexandra C. Dubinsky, Hannah C. Farnsworth, Richard Hakim, Sherry Lin, Giona Kleinberg, Keiramarie Robertson, Canaria Park, Alyssa Solberg, Yechan Yang, Caroline Baynard, Naeem M. Nadaf, Celia C. Beron, Allison E. Girasole, Lynne Chantranupong, Marissa D. Cortopassi, Shannon Prouty, Ludwig Geistlinger, Alexander S. Banks, Thomas S. Scanlan, Sandeep Robert Datta, Michael E. Greenberg, Gabriella L. Boulting, Evan Z. Macosko, Bernardo L. Sabatini
Issue&Volume: 2024-08-22
Abstract: Animals adapt to environmental conditions by modifying the function of their internal organs, including the brain. To be adaptive, alterations in behavior must be coordinated with the functional state of organs throughout the body. Here, we find that thyroid hormone—a regulator of metabolism in many peripheral organs—directly activates cell-type-specific transcriptional programs in the frontal cortex of adult male mice. These programs are enriched for axon-guidance genes in glutamatergic projection neurons, synaptic regulatory genes in both astrocytes and neurons, and pro-myelination factors in oligodendrocytes, suggesting widespread plasticity of cortical circuits. Indeed, whole-cell electrophysiology revealed that thyroid hormone alters excitatory and inhibitory synaptic transmission, an effect that requires thyroid hormone-induced gene regulatory programs in presynaptic neurons. Furthermore, thyroid hormone action in the frontal cortex regulates innate exploratory behaviors and causally promotes exploratory decision-making. Thus, thyroid hormone acts directly on the cerebral cortex in males to coordinate exploratory behaviors with whole-body metabolic state.
DOI: 10.1016/j.cell.2024.07.041
Source:https://www.cell.com/cell/fulltext/S0092-8674(24)00835-3