RETRACTED ARTICLE: Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism
Open accessAbstract
Mental health disorders are manifested in families, yet cannot be fully explained by classical Mendelian genetics. Changes in gene expression via epigenetics present a plausible mechanism. Anxiety often leads to avoidant behaviors which upon repetition may become habitual, maladaptive and resistant to extinction as observed in obsessive compulsive disorders (OCD). Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum, DLS) may be causally linked. The amygdala activates spiny projection neurons in the DLS. Repetitive amygdala terminal stimulation in the DLS elicits long term OCD-like behavior in mice associated with circuitry changes and gene methylation-mediated decrease in the activity of protein phosphatase 1 (PP1). Treatment of OCD-like grooming behavior in Slitrk5, SAPAP3, and laser-stimulated mice with one dose of RG108 (DNA methyltransferase inhibitor), lead to marked symptom improvement lasting for at least one week as well as complete reversal of anomalous changes in circuitry and PP1 gene methylation.
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Studies that have used Sapap3-KO mice to test treatment approaches for OCD remain limited.
“Despite construct, face and predictive validity of the Sapap3-KO mouse model, studies that have used Sapap3-KO mice to test treatment approaches for OCD remain limited [17,18].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [18]
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References 83 · Cited by 11
Research works printed but not linked: 1
- [69]Hebb, D. O. The organization of behavior; a neuropsychological theory. (Wiley, 1949).
- Authors
- Todorov, G., Mayilvahanan, K., Ashurov, D., & Cunha, C.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- Stony Brook School (US)
- Corresponding author
- Cunha, Catarina
- Venue
- Scientific Reports
- Published
- 2019-06-19
- Volume
- 9
- Issue
- 1
- Pages
- 8741-8741
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6584622
- OpenAlex
- W2953215097
- Cited by
- 11
- References
- 83
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 2 · 2020: 5
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2021-02-23)
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- obsessive-compulsive disorder, epigenetics, hypomethylating agents, RG108, protein phosphatase 1, DNA methylation, amygdala, dorsolateral striatum, avoidance behavior, grooming, mouse model
- MeSH terms
- Animals, Compulsive Behavior, Disease Models, Animal, Female, Humans, Male, Obsessive-Compulsive Disorder, Phthalimides, Tryptophan, DNA Methylation, Epigenesis, Genetic, Mice
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