MicroRNA-29 acutely regulates memory stability, expression of synaptic genes, and DNA methylation in the mouse adult hippocampus.

Overview

Authors: Aurelia Viglione^1,2, Chiara Giannuzzi¹, Elena Putignano³, Raffaele Mario Mazziotti^3,4,5, Sara Bagnoli¹, Paola Tognini^6,7,8, Alessandro Cellerino^1,9, Tommaso Pizzorusso^1,3

ORCID iDs: Aurelia Viglione, Tommaso Pizzorusso

Institutions: Scuola Normale Superiore (Italy); Istituto Superiore di Sanità (Italy); Neuroscience Institute (Italy); National Research Council (Italy); Fondazione Stella Maris (Italy); University of Florence (Italy); Scuola Superiore Sant'Anna (Italy); Fondazione Toscana Gabriele Monasterio (Italy); Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (Germany)

Journal: Cellular and molecular life sciences : CMLS, volume 83, issue 1, article 268

Dates: received 25 November 2024; accepted 8 April 2026; published online 12 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1007/s00018-026-06235-9 · PMID 42120714 · PMCID PMC13338005 · OpenAlex W7160925333

Open access: gold, a free copy (OpenAlex)

Status: code on request

Categories: genetics / omics (modality), mouse (organism), cellular / molecular (subfield)

Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, Machine learning, fMRI & imaging, Physiology & signal measures

Keywords: Fear conditioning, Epigenetics, Non-coding RNA, MicroRNA, Hippocampus, Neural plasticity, Cognitive decline, Aging

MeSH: DNA Methylation*, Hippocampus*, Memory*, MicroRNAs*, Synapses*, Aging, Animals, DNA (Cytosine-5-)-Methyltransferases, DNA Methyltransferase 3A, Fear, Gene Expression Regulation, Male, Mice, Mice, Inbred C57BL, Neuronal Plasticity (* major topic)

Topic: MicroRNA in disease regulation (Cancer Research, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: Scuola Normale Superiore

Citations: not cited yet (Europe PMC); 81 references in the paper

Abstract

MicroRNAs are key regulators of brain gene expression, with miR-29 family notably upregulated from development to adulthood and in aging, and showing links to cognitive decline. However, the extent to which miR-29 levels influence learning and memory processes, and its molecular mediators, remains to be determined. Here, we down- and up-regulated miR-29 levels in the dorsal hippocampus of adult mice to reveal miR-29 role in memory. Inhibition of miR-29 enhanced trace fear memory stability, increased Dnmt3a levels, and promoted DNA methylation in a DNMT3a-dependent manner. In contrast, increasing miR-29 impaired memory performances and decreased Dnmt3a levels, suggesting a destabilization of memory processes. Proteomic and transcriptomic analysis demonstrated that miR-29 antagonism upregulated RNA-binding and synaptic proteins and downregulated inflammation and myelin associated proteins. These results underscore miR-29’s pivotal role in memory persistence, plasticity, and cognitive aging, suggesting that miR-29 modulation could offer potential strategies for cognitive enhancement and age-related memory decline.

Supplementary Information: The online version contains supplementary material available at 10.1007/s00018-026-06235-9.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data Availability Statement

Further information and requests for resources and reagents should be directed to the lead contact, Tommaso Pizzorusso.

All data reported in the main text or supplemental information are available from the lead contact upon request. All original code is also available from the lead contact upon request. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

This study did not generate new unique reagents.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 8 keywords, 15 MeSH terms, 1 funder, 79 references.

Cite

This paper

Viglione, A., Giannuzzi, C., Putignano, E., Mazziotti, R. M., Bagnoli, S., Tognini, P., Cellerino, A., & Pizzorusso, T. (2026). MicroRNA-29 acutely regulates memory stability, expression of synaptic genes, and DNA methylation in the mouse adult hippocampus. Cellular and molecular life sciences : CMLS, 83(1), 268. https://doi.org/10.1007/s00018-026-06235-9

BibTeX

@article{viglione2026microrna, author = {Viglione, Aurelia and Giannuzzi, Chiara and Putignano, Elena and Mazziotti, Raffaele Mario and Bagnoli, Sara and Tognini, Paola and Cellerino, Alessandro and Pizzorusso, Tommaso}, title = {{MicroRNA-29 acutely regulates memory stability, expression of synaptic genes, and DNA methylation in the mouse adult hippocampus}}, journal = {Cellular and molecular life sciences : CMLS}, year = {2026}, month = may, volume = {83}, number = {1}, pages = {268}, publisher = {Springer}, issn = {1420-682X}, doi = {10.1007/s00018-026-06235-9}, url = {https://doi.org/10.1007/s00018-026-06235-9}, pmid = {42120714}, pmcid = {PMC13338005} }

RIS

TY - JOUR AU - Viglione, Aurelia AU - Giannuzzi, Chiara AU - Putignano, Elena AU - Mazziotti, Raffaele Mario AU - Bagnoli, Sara AU - Tognini, Paola AU - Cellerino, Alessandro AU - Pizzorusso, Tommaso TI - MicroRNA-29 acutely regulates memory stability, expression of synaptic genes, and DNA methylation in the mouse adult hippocampus T2 - Cellular and molecular life sciences : CMLS J2 - Cell Mol Life Sci PY - 2026 DA - 2026/05/12 VL - 83 IS - 1 SP - 268 SN - 1420-682X PB - Springer DO - 10.1007/s00018-026-06235-9 UR - https://doi.org/10.1007/s00018-026-06235-9 LA - en ER -

CSL-JSON

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