前頭皮質神経細胞の繊毛が動物のストレス反応を調整する新たな機能を発見(Song-Hai Shi’s group reveals novel function of prefrontal cortical neuron primary cilia in modulating animal stress)

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2025-04-06 清華大学

前頭皮質神経細胞の繊毛が動物のストレス反応を調整する新たな機能を発見(Song-Hai Shi’s group reveals novel function of prefrontal cortical neuron primary cilia in modulating animal stress)Figure 1. Prefrontal cortical neuron primary cilia modulate animal stress

清華大学の石宋海(Song-Hai Shi)教授の研究チームは、前頭前野皮質の興奮性ニューロンに存在する一次繊毛が、動物のストレス応答を調節する重要な役割を果たすことを明らかにしました。マウスを用いた研究で、ストレス刺激に応じて前頭前野の一次繊毛が一貫して伸長することが観察されました。さらに、前頭前野の興奮性ニューロンから一次繊毛を選択的に除去すると、ストレス感受性と応答が低下することが示されました。この研究は、ストレス関連障害の理解と治療に新たな視点を提供するものです。

<関連情報>

前頭前野における一次繊毛プロテインキナーゼA活性がマウスのストレスを調節する Primary ciliary protein kinase A activity in the prefrontal cortex modulates stress in mice

Jiajun Yang ∙ Yingjie Dong ∙ Jie Liu,∙ … ∙ Jian Ma ∙ Hang Shi, ∙ Song-Hai Shi
Neuron  Published:March 7, 2025
DOI:https://doi.org/10.1016/j.neuron.2025.02.002

Highlights

  • Various animal stressors prolong neuronal primary cilia in the PFC
  • Removal of PFC excitatory neuron primary cilia suppresses animal stress
  • Corticosterone treatment triggers primary ciliary cAMP elevation in PFC neurons
  • Primary ciliary PKA activity suppression in PFC neurons reduces animal stress

Summary

Primary cilia are cellular antennae emanating from vertebrate cell surfaces to sense and transduce extracellular signals intracellularly to regulate cell behavior and function. However, their signal sensing and physiological functions in neocortical neurons remain largely unclear. Here, we show that, in response to various animal stressors, primary cilia in the mouse prefrontal cortex (PFC) exhibit consistent axonemal elongation. Selective removal of excitatory neuron primary cilia in the prefrontal but not sensory cortex leads to a reduction in animal stress sensing and response. Treatment with corticosterone, the major stress hormone, elicits an increase in primary ciliary cyclic adenosine 3′,5′-monphosphate (cAMP) level in PFC excitatory neurons and a decrease in neuronal excitability dependent on primary cilia. Suppression of primary ciliary protein kinase A (PKA) activity in PFC excitatory neurons reduces animal stress. These results suggest that excitatory neurons in the PFC are involved in sensing and regulating animal stress via primary ciliary cAMP/PKA signaling.

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