Age-dependent attenuation of spatial memory deficits by the histone acetyltransferase p300/CBP-associated factor (PCAF) in 3xTG Alzheimer's disease mice.


Journal

Learning & memory (Cold Spring Harbor, N.Y.)
ISSN: 1549-5485
Titre abrégé: Learn Mem
Pays: United States
ID NLM: 9435678

Informations de publication

Date de publication:
03 2022
Historique:
received: 13 10 2021
accepted: 04 01 2022
entrez: 16 2 2022
pubmed: 17 2 2022
medline: 20 4 2022
Statut: epublish

Résumé

Histone acetylation, catalyzed by histone acetyltransferases, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF remediated memory impairments in 3xTG-AD mice in an age-related bidirectional manner. At 3 and 6 mo of age, PCAF activation ameliorated memory deficits. At 9 mo of age, PCAF activation had no effect on spatial memory, whereas PCAF inhibition improved memory deficits in females. This work reveals a complex potential therapeutic role for PCAF in AD, initially benefitting memory but becoming detrimental as the disease progresses.

Identifiants

pubmed: 35169045
pii: 29/3/71
doi: 10.1101/lm.053536.121
pmc: PMC8852226
doi:

Substances chimiques

Histone Acetyltransferases EC 2.3.1.48
p300-CBP Transcription Factors EC 2.3.1.48
p300-CBP-associated factor EC 2.3.1.48

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

71-76

Informations de copyright

© 2022 Creighton et al.; Published by Cold Spring Harbor Laboratory Press.

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Auteurs

Samantha D Creighton (SD)

Department of Psychology, Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada.

Kristen H Jardine (KH)

Department of Psychology, Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario N1G 2W1, Canada.

Alexa Desimone (A)

Department of Psychology, Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario N1G 2W1, Canada.

Megan Zmetana (M)

Department of Psychology, Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario N1G 2W1, Canada.

Sabrina Castellano (S)

Department of Pharmacy, Epigenetic Med Chem Laboratory, University of Salerno, I-84084 Fisciano, Salerno, Italy.

Ciro Milite (C)

Department of Pharmacy, Epigenetic Med Chem Laboratory, University of Salerno, I-84084 Fisciano, Salerno, Italy.

Gianluca Sbardella (G)

Department of Pharmacy, Epigenetic Med Chem Laboratory, University of Salerno, I-84084 Fisciano, Salerno, Italy.

Boyer D Winters (BD)

Department of Psychology, Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario N1G 2W1, Canada.

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Classifications MeSH