体对脑胰岛素和Notch信号通过神经元CREB活动调节记忆。

IF 19.4 Q1 CELL BIOLOGY
Nature aging Pub Date : 2025-07-01 Epub Date: 2025-05-27 DOI:10.1038/s43587-025-00873-7
Shiyi Zhou, Katherine E Novak, Rachel Kaletsky, Yifei Weng, Jonathan St Ange, Morgan E Stevenson, Erik Toraason, Yanping Zhang, Wenhong Zhang, Meng-Qiu Dong, Coleen T Murphy
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引用次数: 0

摘要

虽然记忆调节主要被认为是神经元自主的,但大脑外的因素也会影响神经元的功能。在秀丽隐杆线虫中,胰岛素/IGF-1样信号通路(IIS)调节寿命、代谢和记忆:长寿命daf-2胰岛素/IGF-1受体突变体在单次训练后记忆持续时间增加一倍以上,并且假设记忆调节严格是神经元的。然而,我们在这里发现,DAF-2在皮下的降解也通过扩散的Notch配体OSM-11的表达极大地延长了记忆,OSM-11反过来激活神经元中的Notch信号。神经元的单核RNA测序显示CREB和其他记忆基因的表达增加。此外,在老年动物中,皮下is - notch通路的激活以及OSM-11的过表达通过CREB活性来拯救记忆和学习。因此,样肝下皮层中的胰岛素信号非自主地调节神经元功能,通过从身体到大脑的is - notch - creb信号提供代谢和记忆之间的系统连接。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity.

While memory regulation is predominantly understood as autonomous to neurons, factors outside the brain can also affect neuronal function. In Caenorhabditis elegans, the insulin/IGF-1-like signaling (IIS) pathway regulates longevity, metabolism and memory: long-lived daf-2 insulin/IGF-1 receptor mutants more than double memory duration after a single training session, and it was assumed that memory regulation was strictly neuronal. However, here we show that degradation of DAF-2 in the hypodermis also greatly extends memory, via expression of the diffusible Notch ligand, OSM-11, which in turn activates Notch signaling in neurons. Single-nucleus RNA sequencing of neurons revealed increased expression of CREB and other memory genes. Furthermore, in aged animals, activation of the hypodermal IIS-Notch pathway as well as OSM-11 overexpression rescue both memory and learning via CREB activity. Thus, insulin signaling in the liver-like hypodermis non-autonomously regulates neuronal function, providing a systemic connection between metabolism and memory through IIS-Notch-CREB signaling from the body to the brain.

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