The role of the m6A/m demethylase FTO in memory is both task and sex-dependent in mice.

Autor: Leonetti AM; Department of Biology, University of Toronto Mississauga, Mississauga, ON, L5L 1C6, Canada; Department of Cell & Systems Biology, University of Toronto, Toronto, ON, M5S 3G3, Canada; Department of Psychology, University of Toronto Mississauga, Mississauga, ON, L5L 1C6, Canada; Department of Biological Sciences, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON, L2S 3A1, Canada. Electronic address: al13gs@brocku.ca., Galluzzo IR; Department of Cell & Systems Biology, University of Toronto, Toronto, ON, M5S 3G3, Canada. Electronic address: isabella.galluzzo@mail.utoronto.ca., McLean TAD; Department of Cell & Systems Biology, University of Toronto, Toronto, ON, M5S 3G3, Canada. Electronic address: timothy.mclean@mail.utoronto.ca., Stefanelli G; Department of Biology, University of Ottawa, Ottawa, Marie-Curie Private, ON K1N 9A, Canada. Electronic address: gilda.stefanelli@uottawa.ca., Ramnaraign F; Department of Biology, University of Toronto Mississauga, Mississauga, ON, L5L 1C6, Canada. Electronic address: framnaraign@uvic.ca., Holm S; Department of Biology, University of Toronto Mississauga, Mississauga, ON, L5L 1C6, Canada. Electronic address: samuelholm93@gmail.com., Winston SM; Department of Surgery, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA; Graduate School of Biomedical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: framnaraign@uvic.ca., Reeves IL; Department of Surgery, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA; Graduate School of Biomedical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: isaiah.reeves@stjude.org., Brimble MA; Dept of Host-Microbe Interactions, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA. Electronic address: mark.brimble@stjude.org., Walters BJ; Department of Biology, University of Toronto Mississauga, Mississauga, ON, L5L 1C6, Canada; Department of Cell & Systems Biology, University of Toronto, Toronto, ON, M5S 3G3, Canada. Electronic address: BrandonJ.Walters@utoronto.ca.
Jazyk: angličtina
Zdroj: Neurobiology of learning and memory [Neurobiol Learn Mem] 2024 Apr; Vol. 210, pp. 107903. Date of Electronic Publication: 2024 Feb 23.
DOI: 10.1016/j.nlm.2024.107903
Abstrakt: Formation of long-term memories requires learning-induced changes in both transcription and translation. Epitranscriptomic modifications of RNA recently emerged as critical regulators of RNA dynamics, whereby adenosine methylation (m6A) regulates translation, mRNA stability, mRNA localization, and memory formation. Prior work demonstrated a pro-memory phenotype of m6A, as loss of m6A impairs and loss of the m6A/m demethylase FTO improves memory formation. Critically, these experiments focused exclusively on aversive memory tasks and were only performed in male mice. Here we show that the task type and sex of the animal alter effects of m6A on memory, whereby FTO-depletion impaired object location memory in male mice, in contrast to the previously reported beneficial effects of FTO depletion on aversive memory. Additionally, we show that female mice have no change in performance after FTO depletion, demonstrating that sex of the mouse is a critical variable for understanding how m6A contributes to memory formation. Our study provides the first evidence for FTO regulation of non-aversive spatial memory and sexspecific effects of m6A, suggesting that identification of differentially methylated targets in each sex and task will be critical for understanding how epitranscriptomic modifications regulate memory.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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