Epigenetic alterations regulate estradiol-induced enhancement of memory consolidation.
The involvement of epigenetic alterations in mediating effects of estrogens on memory is unknown. The present study determined whether histone acetylation and DNA methylation are critical for the potent estrogen 17beta-estradiol (E(2)) to enhance object recognition memory. We show that dorsal hippocampal E(2) infusion increases acetylation of dorsal hippocampal histone H3, but not H4--an effect blocked by dorsal hippocampal inhibition of ERK activation. Further, intrahippocampal inhibition of ERK activation or DNA methyltransferase (DNMT) activity blocked the memory-enhancing effects of E(2). Consistent with these effects, E(2) decreased levels of HDAC2 protein and increased DNMT expression in the dorsal hippocampus. These findings provide evidence that the beneficial effects of E(2) on memory consolidation are associated with epigenetic alterations, and suggest these can be triggered by dorsal hippocampal ERK signaling.
Zhao
Zaorui
Z
Department of Psychology and Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA.
Fan
Lu
L
Frick
Karyn M
KM
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D056284:Histone Deacetylase 1 / Q000235:genetics; D056464:Histone Deacetylase 2 / Q000235:genetics; D006657:Histones / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D006657:Histones; D012333:RNA, Messenger; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2