| 著者 |
Zhou S, Novak KE, Kaletsky R, Weng Y, Ange JS, Stevenson ME, Toraason E, Zhang Y, Zhang W, Dong MQ, Murphy CT.
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| Abstract |
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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