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bioRxiv · 10.1101/2024.11.12.623333

Bidirectional Impact of miR-29a modulation on Memory Stability in the Adult Brain

Viglione, A.·Giannuzzi, C.·Putignano, E.·Mazziotti, R.·Cellerino, A. M.·Pizzorusso, T.
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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-29s 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.

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Viglione, A., Giannuzzi, C., Putignano, E., Mazziotti, R., Cellerino, A. M., Pizzorusso, T.. 2024-11-14. Bidirectional Impact of miR-29a modulation on Memory Stability in the Adult Brain. https://doi.org/10.1101/2024.11.12.623333

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