Reference - Detail
| RRC ID | 88074 |
|---|---|
| Author | Zhou S, Novak KE, Kaletsky R, Weng Y, Ange JS, Stevenson ME, Toraason E, Zhang Y, Zhang W, Dong MQ, Murphy CT. |
| Title | Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity. |
| Journal | Nat Aging |
| 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. |
| Volume | 5(7) |
| Pages | 1232-1248 |
| Published | 2025-7-1 |
| DOI | 10.1038/s43587-025-00873-7 |
| PII | 10.1038/s43587-025-00873-7 |
| PMID | 40425807 |
| PMC | PMC12270903 |
| MeSH | Animals Brain* / metabolism Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cyclic AMP Response Element-Binding Protein* / metabolism Insulin* / metabolism Memory* / physiology Neurons* / metabolism Receptor, Insulin / metabolism Receptors, Notch* / genetics Receptors, Notch* / metabolism Signal Transduction* / physiology |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 24 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm5155 |