Cognition and mood-related behaviors in L3mbtl1 null mutant mice
Open accessAbstract
Alterations in histone lysine methylation and epigenetic regulators of gene expression could play a role in the neurobiology and treatment of patients diagnosed with mood spectrum disorder, including depression and anxiety. Mutations and altered expression of various lysine methyltransferases (KMTs) and demethylases (KDMs) have been linked to changes in motivational and emotional behaviors in preclinical model systems. However, it is not known whether regulators operating downstream of histone lysine methylation could affect mood-related behavior. Malignant Brain Tumor (MBT) domain 'chromatin reader' proteins bind to methylated histone lysine residues and associate with chromatin remodeling complexes to facilitate or repress gene expression. MBT proteins, including the founding member, L3mbtl1, maintain high levels of expression in neurons of the mature brain. Here, we exposed L3mbtl1 null mutant mice to a wide range of tests exploring cognition and mood-relevant behaviors at baseline and in the context of social isolation, as a stressor to elicit depression-related behavior in susceptible mice. L3mbtl1 loss-of-function was associated with significant decreases in depression and and anxiety in some of the behavioral paradigms. This was not associated with a more generalized neurological dysfunction because cognition and memory remained unaltered in comparison to controls. These findings warrant further investigations on the role of MBT chromatin reader proteins in the context of emotional and affective behaviors.
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Histone demethylases (KDMs) participate in emotional regulation.
“Histone demethylases (KDMs) also participate in emotional regulation (Shen et al., 2015).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Shen et al., 2015
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- Authors
- Shen, E. Y., Jiang, Y., Mao, W., Futai, K., Hock, H., & Akbarian, S.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- University of Massachusetts Chan Medical School (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Akbarian, Schahram
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-04-07
- Volume
- 10
- Issue
- 4
- Pages
- e0121252
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4388653
- OpenAlex
- W2094209767
- Cited by
- 4
- References
- 61
- Citations by year
- 2026: 1 · 2019: 1 · 2018: 1 · 2017: 1
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute of Mental Health (P50MH096890, R01MH086509)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- L3MBTL1, chromatin reader proteins, histone lysine methylation, depression, anxiety, social isolation, stress, cognition, memory, chromatin remodeling
- MeSH terms
- Affect, Animals, Behavior, Animal, Cognition, Depression, Memory, Mice, Mutant Strains, Nuclear Proteins, Repressor Proteins, Tumor Suppressor Proteins, Mice
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