Pharmacological HDAC3 inhibition alters memory updating in young and old male mice.

Autor:	Smies CW; Department of Biology, Pennsylvania State University, University Park, PA, United States.; Center for the Molecular Investigation of Neurological Disorders (CMIND), The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States., Bellfy L; Department of Biology, Pennsylvania State University, University Park, PA, United States.; Center for the Molecular Investigation of Neurological Disorders (CMIND), The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States., Wright DS; Department of Biology, Pennsylvania State University, University Park, PA, United States.; Center for the Molecular Investigation of Neurological Disorders (CMIND), The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States., Bennetts SG; Department of Biology, Pennsylvania State University, University Park, PA, United States.; Center for the Molecular Investigation of Neurological Disorders (CMIND), The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States., Urban MW; Department of Biology, Pennsylvania State University, University Park, PA, United States.; Center for the Molecular Investigation of Neurological Disorders (CMIND), The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States., Brunswick CA; Department of Biology, Pennsylvania State University, University Park, PA, United States.; Center for the Molecular Investigation of Neurological Disorders (CMIND), The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States., Shu G; Department of Biology, Pennsylvania State University, University Park, PA, United States.; Center for the Molecular Investigation of Neurological Disorders (CMIND), The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States., Kwapis JL; Department of Biology, Pennsylvania State University, University Park, PA, United States.; Center for the Molecular Investigation of Neurological Disorders (CMIND), The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2024 Jun 26; Vol. 17, pp. 1429880. Date of Electronic Publication: 2024 Jun 26 (Print Publication: 2024).
DOI:	10.3389/fnmol.2024.1429880
Abstrakt:	Long-term memories are not stored in a stable state but must be flexible and dynamic to maintain relevance in response to new information. Existing memories are thought to be updated through the process of reconsolidation, in which memory retrieval initiates destabilization and updating to incorporate new information. Memory updating is impaired in old age, yet little is known about the mechanisms that go awry. One potential mechanism is the repressive histone deacetylase 3 (HDAC3), which is a powerful negative regulator of memory formation that contributes to age-related impairments in memory formation. Here, we tested whether HDAC3 also contributes to age-related impairments in memory updating using the Objects in Updated Locations (OUL) paradigm. We show that blocking HDAC3 immediately after updating with the pharmacological inhibitor RGFP966 ameliorated age-related impairments in memory updating in 18-m.o. male mice. Surprisingly, we found that post-update HDAC3 inhibition in young (3-m.o.) male mice had no effect on memory updating but instead impaired memory for the original information, suggesting that the original and updated information may compete for expression at test and HDAC3 helps regulate which information is expressed. To test this idea, we next assessed whether HDAC3 inhibition would improve memory updating in young male mice given a weak, subthreshold update. Consistent with our hypothesis, we found that HDAC3 blockade strengthened the subthreshold update without impairing memory for the original information, enabling balanced expression of the original and updated information. Together, this research suggests that HDAC3 may contribute to age-related impairments in memory updating and may regulate the strength of a memory update in young mice, shifting the balance between the original and updated information at test. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Smies, Bellfy, Wright, Bennetts, Urban, Brunswick, Shu and Kwapis.)
Databáze:	MEDLINE
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