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Hippocampal Histone Acetylation Regulates Object Recognition and the Estradiol-Induced Enhancement of Object Recognition
Open accessAbstract
Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitor in vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol E2. We first showed that bilateral infusion of garcinol (0.1, 1, or 10 μg/side) into the dorsal hippocampus (DH) immediately after training impaired object recognition memory consolidation in ovariectomized female mice. A behaviorally effective dose of garcinol (10 μg/side) also significantly decreased DH HAT activity. We next examined whether DH infusion of a behaviorally subeffective dose of garcinol (1 ng/side) could block the effects of DH E2 infusion on object recognition and epigenetic processes. Immediately after training, ovariectomized female mice received bilateral DH infusions of vehicle, E2 (5 μg/side), garcinol (1 ng/side), or E2 plus garcinol. Forty-eight hours later, garcinol blocked the memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in DH histone H3 acetylation, HAT activity, and levels of the de novo methyltransferase DNMT3B, as well as the E2-induced decrease in levels of the memory repressor protein histone deacetylase 2. Collectively, these findings suggest that histone acetylation is critical for object recognition memory consolidation and the beneficial effects of E2 on object recognition. Importantly, this work demonstrates that the role of histone acetylation in memory processes can be studied using a HAT inhibitor.
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“Post-sample hippocampal infusions of histone acetylase inhibitors decreased histone acetylation and impaired NOP memory”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Zhao et al., 2012
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Metadata
- Authors
- Zhao, Z., Fan, L., Fortress, A. M., Boulware, M. I., & Frick, K. M.
- Affiliations
- Yale University (US)
- University of Wisconsin–Milwaukee (US)
- Corresponding author
- Frick, Karyn M.
- ORCID
- Frick, Karyn M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-02-14
- Volume
- 32
- Issue
- 7
- Pages
- 2344-2351
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3401048
- OpenAlex
- W1970636571
- Cited by
- 115
- References
- 46
- Citations by year
- 2025: 3 · 2024: 8 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 11 · 2019: 10 · 2018: 12 · 2017: 6 · 2016: 16 · 2015: 8 · 2014: 12 · 2013: 16 · 2012: 3
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- University of Wisconsin-Milwaukee
- National Institute on Aging (R01AG022525, AG022525)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- histone acetylation, histone acetyltransferase inhibition, garcinol, object recognition memory, memory consolidation, estradiol, hippocampus, dorsal hippocampus, histone H3 acetylation, DNMT3B, HDAC2
- MeSH terms
- Acetylation, Animals, Estradiol, Female, Hippocampus, Histones, Mice, Inbred C57BL, Plant Extracts, Terpenes, Recognition, Psychology, Mice, Histone Acetyltransferases
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