Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition. J Neurosci 2012 Feb 15;32(7):2344-51
Date
03/08/2012Pubmed ID
22396409Pubmed Central ID
PMC3401048DOI
10.1523/JNEUROSCI.5819-11.2012Scopus ID
2-s2.0-84857090793 (requires institutional sign-in at Scopus site) 114 CitationsAbstract
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.
Author List
Zhao Z, Fan L, Fortress AM, Boulware MI, Frick KMAuthors
Karyn Frick BA,MA,PhD Professor in the Psychology department at University of Wisconsin - MilwaukeeMarissa Iden Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AcetylationAnimals
Estradiol
Female
Hippocampus
Histone Acetyltransferases
Histones
Mice
Mice, Inbred C57BL
Plant Extracts
Terpenes
