Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice

Bjorge, Monica D., Hildrestrand, Gunn A., Scheffler, Katja, Suganthan, Rajikala, Rolseth, Veslemoy, Kusnierczyk, Anna, Rowe, Alexander D., Vagbo, Cathrine B., Vetlesen, Susanne, Eide, Lars, Slupphaug, Geir, Nakabeppu, Yusaku, Bredy, Timothy W., Klungland, Arne and Bjoras, Magnar (2015) Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice. Cell Reports, 13 12: 2671-2678. doi:10.1016/j.celrep.2015.12.001


Author Bjorge, Monica D.
Hildrestrand, Gunn A.
Scheffler, Katja
Suganthan, Rajikala
Rolseth, Veslemoy
Kusnierczyk, Anna
Rowe, Alexander D.
Vagbo, Cathrine B.
Vetlesen, Susanne
Eide, Lars
Slupphaug, Geir
Nakabeppu, Yusaku
Bredy, Timothy W.
Klungland, Arne
Bjoras, Magnar
Title Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice
Journal name Cell Reports   Check publisher's open access policy
ISSN 2211-1247
Publication date 2015-12-29
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.celrep.2015.12.001
Open Access Status DOI
Volume 13
Issue 12
Start page 2671
End page 2678
Total pages 8
Place of publication New York, NY, United States
Publisher Elsevier
Language eng
Formatted abstract
Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic DNA lesion associated with cognitive decline. We have examined behavior and cognitive function in mice deficient of these glycosylases. Ogg1−/−Mutyh−/− mice were more active and less anxious, with impaired learning ability. In contrast, Mutyh−/− mice showed moderately improved memory. We observed no apparent change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutants belong to pathways known to be involved in anxiety and cognition. Esr1 targets were upregulated, suggesting a role of Ogg1 and Mutyh in repression of Esr1 signaling. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh regulate hippocampal gene expression related to cognition and behavior, suggesting a role for the glycosylases in regulating adaptive behavior.
Keyword Oxidative Damage
Lesion 8-Hydroxyguanine
Mitochondrial-Dna
Null Mice
Memory
Disease
Mechanisms
Repair
Methylation
Protects
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
 
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