학술논문
Specific exercise patterns generate an epigenetic molecular memory window that drives long-term memory formation and identifies ACVR1C as a bidirectional regulator of memory in mice
Document Type
article
Author
Ashley A. Keiser; Tri N. Dong; Enikö A. Kramár; Christopher W. Butler; Siwei Chen; Dina P. Matheos; Jacob S. Rounds; Alyssa Rodriguez; Joy H. Beardwood; Agatha S. Augustynski; Ameer Al-Shammari; Yasaman Alaghband; Vanessa Alizo Vera; Nicole C. Berchtold; Sharmin Shanur; Pierre Baldi; Carl W. Cotman; Marcelo A. Wood
Source
Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024)
Subject
Language
English
ISSN
2041-1723
Abstract
Abstract Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.