Faculty Collaboration Database

17β-Estradiol regulates histone alterations associated with memory consolidation and increases Bdnf promoter acetylation in middle-aged female mice. Learn Mem 2014 Sep;21(9):457-67

Date

08/17/2014

Pubmed ID

25128537

Pubmed Central ID

PMC4138358

DOI

10.1101/lm.034033.113

Scopus ID

2-s2.0-84907750752 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

Histone acetylation is essential for hippocampal memory formation in young adult rodents. Although dysfunctional histone acetylation has been associated with age-related memory decline in male rodents, little is known about whether histone acetylation is altered by aging in female rodents. In young female mice, the ability of 17β-estradiol (E2) to enhance object recognition memory consolidation requires histone H3 acetylation in the dorsal hippocampus. However, the extent to which histone acetylation is regulated by E2 in middle-aged females is unknown. The mnemonic benefits of E2 in aging females appear to be greatest in middle age, and so pinpointing the molecular mechanisms through which E2 enhances memory at this age could lead to the development of safer and more effective treatments for maintaining memory function without the side effects of current therapies. Here, we show that dorsal hippocampal infusion of E2 rapidly enhanced object recognition and spatial memory, and increased histone H3 acetylation in the dorsal hippocampus, while also significantly reducing levels of histone deacetylase (HDAC2 and HDAC3) proteins. E2 specifically increased histone H3 acetylation at Bdnf promoters pII and pIV in the dorsal hippocampus of both young and middle-aged mice, despite age-related decreases in pI and pIV acetylation. Furthermore, levels of mature BDNF and pro-BDNF proteins in the dorsal hippocampus were increased by E2 in middle-aged females. Together, these data suggest that the middle-aged female dorsal hippocampus remains epigenetically responsive to E2, and that E2 may enhance memory in middle-aged females via epigenetic regulation of Bdnf.

Author List

Fortress AM, Kim J, Poole RL, Gould TJ, Frick KM

Author

Karyn Frick BA,MA,PhD Professor in the Psychology department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Acetylation
Animals
Brain-Derived Neurotrophic Factor
Epigenesis, Genetic
Estradiol
Female
Hippocampus
Histone Deacetylase 2
Histone Deacetylases
Histones
Memory
Mice
Promoter Regions, Genetic