| 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
|
| Resource |
| C.elegans |
tm5155 |
