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Cited by 64Epigenetics and DNA MethylationNeurotransmitter Receptor Influence on BehaviorMemory and Neural Mechanisms

Impact of DNMT1 and DNMT3a forebrain knockout on depressive- and anxiety like behavior in mice

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Morris, Michael J., Na, Elisa S., Autry, Anita E., Monteggia, Lisa M.·2016·Neurobiology of Learning and Memory
DOI 10.1016/j.nlm.2016.08.012PMC PMC5050143
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Abstract

DNA methylation has been shown to impact certain forms of synaptic and behavioral plasticity that have been implicated in the development in psychiatric disorders. DNA methylation is catalyzed by DNA methyltransferase (DNMT) enzymes that continue to be expressed in postmitotic neurons in the forebrain. Using a conditional forebrain knockout of DNMT1 or DNMT3a we assessed the role of these DNMTs in anxiety and depressive-like behavior in mice using an array of behavioral testing paradigms. Forebrain deletion of DNMT1 had anxiolytic and antidepressant-like properties as assessed by elevated plus maze, novelty suppressed feeding, forced swim, and social interaction tests. DNMT3a knockout mice, by contrast, did not exhibit significant behavioral alterations in these tests. Given the putative role of altered DNA methylation patterns in the development of schizophrenia, we also assessed DNMT1 and DNMT3a knockout mice in a prepulse inhibition task and found an enhanced prepulse inhibition of startle in DNMT1 knockouts relative to wild type mice, with no change evident in DNMT3a knockout mice. Our data suggest that DNMT1 and DNMT3a are distinctly involved in affective behavior and that DNMT1 may ultimately represent a potential target for treatment of certain affective behavioral disorders.

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  • The DNA methylation reaction is catalyzed by DNA methyltransferases, composed of DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L.

    “This reaction is catalyzed by a large class of enzymes known as DNA methyltransferases (DNMTs), composed of DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L (Morris et al., 2016).”

    From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Morris et al., 2016

    The Introduction states that DNA methyltransferases catalyze transfer of a methyl group to cytosine and identifies DNMT1, DNMT3a, and DNMT3b. It does not identify DNMT2 or DNMT3L, so the full five-member list attributed to this paper is not supported by our copy. (LLM, conf=0.88)

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Authors
Morris, M. J., Na, E. S., Autry, A. E., & Monteggia, L. M.
Affiliations
  • Texas Woman's University (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Monteggia, Lisa M.
ORCID
Venue
Neurobiology of Learning and Memory
Publisher
Elsevier BV
Published
2016-11
Volume
135
Pages
139-145
ISSN
1074-7427 (ISSN-L)
DOI
10.1016/j.nlm.2016.08.012
PMC
PMC5050143
OpenAlex
W2514057862
Cited by
64
References
2
Citations by year
2026: 6 · 2025: 1 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 11 · 2019: 5 · 2018: 6 · 2017: 5
FWCI
2.77
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Learning and Memory (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Health (MH081060)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
DNMT1, DNMT3A, DNA methyltransferases, DNA methylation, depression-like behavior, anxiety-like behavior, prepulse inhibition, schizophrenia, mood disorders, neuropsychiatric disorders, synaptic plasticity
MeSH terms
DNA (Cytosine-5-)-Methyltransferase 1, DNA Methyltransferase 3A, Animals, Anxiety, Behavior, Animal, Depression, Disease Models, Animal, DNA (Cytosine-5-)-Methyltransferases, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Prosencephalon, Mice, Knockout, Mice, Mice, 129 Strain, Prepulse Inhibition

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