RETRACTED ARTICLE: Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism

Todorov, German; Mayilvahanan, Karthikeyan; Ashurov, David; Cunha, Catarina

doi:10.1038/s41598-019-45325-6

Cited by 11 publications

(4 citation statements)

References 80 publications

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“…One of the aims of the future work at the Bergen Center for Brain Plasticity is to combine MRI and other biological measures to a contribute to a more integrated view of the psychobiology of OCD and anxiety disorders. We also aim to combine these measures with genetics and epigenetics to better understand how changes in the body and brain are reflected in DNA and its methylation (Todorov, Mayilvahanan, Ashurov, & Cunha, 2019).…”

Section: Implications For Future Researchmentioning

confidence: 99%

Effects of Bergen 4-Day Treatment on Resting-State Graph Features in Obsessive-Compulsive Disorder

Thorsen

Vriend

Wit

et al. 2021

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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It takes a village to raise a child and even more to raise a scientist, and this thesis would not be possible without years of work by my supervisors. I wish to thank Gerd Kvale and Bjarne Hansen for bothering to answer an email from me, a naïve psychology student, in November 2013. I had just received an offer to revise and resubmit my first article by a slightly confused editor who probably didn't understand what to do with a review paper written by a student with no supervisor. Gerd and Bjarne decided to give me a chance to work as a research assistant, which became the first building block of my PhD and our first paper together (Thorsen, van den Heuvel, Hansen, & Kvale, 2015). I wish to thank Bjarne and Gerd for showing how to combine being a caring person, clinician, and scientist. In addition, I thank them for trusting eager new students with important work and for guiding both patients and students to help them prosper. I wish to thank Odile van den Heuvel for her kind, intensive, generous, and enlightening guidance on how to combine living a good life and doing science. I remember travelling to Amsterdam for the first time in June 2014, then an eager and anxious 23-year old. However, my anxiety was soon lifted by Odile, the members of her research group, and her lovely family. I especially wish to thank her for her utmost generosity in inviting to me to live with her and her family for many of my visits to Amsterdam. Words cannot express my gratitude to my supervisors, and I look forward to working and spending time together in the future. I wish to thank my family and friends which make both life and work meaningful. I especially wish to thank Stella J. de Wit for guidance, discussions, and lots of fun throughout my PhD. I also thank her for inviting me to get to know her dear family. My visits to Weesp are very dear to me,

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Section: Implications For Future Researchmentioning

confidence: 99%

Effects of Bergen 4-Day Treatment on Resting-State Graph Features in Obsessive-Compulsive Disorder

Thorsen

Vriend

Wit

et al. 2021

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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“…Two knock-out mice models that generated a phenotype replicating the features observed in patients showed a phenotype very similar to the OCD features observed in patients: the SAPAP3-/- (Welch et al, 2007) and the SLITRK1-/-mice (Katayama et al, 2010), exhibiting increased anxiety and compulsive grooming behaviors. Todorov et al (Todorov et al, 2019) observed that inhibition of DNA methyltransferase in these mice induced marked symptom improvement lasting for at least one week, as well as reversed altered methylation of protein phosphatase 1 gene, which inhibits memory formation and learning (Genoux et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers

Bellia

Vismara

Annunzi

et al. 2021

Journal of Psychiatric Research

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“…Synaptic pruning might also be altered in mice intranasally infected with Group A Streptococcus, which function as a model for PANDAS (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, characterized by sudden onset OCD) [ 54 , 55 ]. Moreover, the offspring of pregnant Sapap3 ko mice injected with the non-nucleoside DNA methyltransferase inhibitor RG108, which affects synaptic pruning, showed a 4-month delay in the development of repetitive grooming behaviour [ 56 ], whereas a similar injection in adult Sapap3 ko mice ameliorated such behaviour for only 3 days [ 57 ]. Parallel, a series of clinical imaging studies suggest abnormal synaptic pruning patterns in, among others, frontostriatal brain structures as a possible explanation for volumetric abnormalities in paediatric OCD patients [ 58 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Sapap3 deletion causes dynamic synaptic density abnormalities: a longitudinal [11C]UCB-J PET study in a model of obsessive–compulsive disorder-like behaviour

et al. 2020

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Background Currently, the evidence on synaptic abnormalities in neuropsychiatric disorders—including obsessive–compulsive disorder (OCD)—is emerging. The newly established positron emission tomography (PET) ligand ((R)-1-((3-((11)C-methyl-(11)C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) ([11C]UCB-J) provides the opportunity to visualize synaptic density changes in vivo, by targeting the synaptic vesicle protein 2A (SV2A). Here, we aim to evaluate such alterations in the brain of the SAP90/PSD-95-associated protein 3 (Sapap3) knockout (ko) mouse model, showing an abnormal corticostriatal neurotransmission resulting in OCD-like behaviour. Methods Longitudinal [11C]UCB-J µPET/CT scans were acquired in Sapap3 ko and wildtype (wt) control mice (n = 9/group) to study SV2A availability. Based on the Logan reference method, we calculated the volume of distribution (VT(IDIF)) for [11C]UCB-J. Both cross-sectional (wt vs. ko) and longitudinal (3 vs. 9 months) volume-of-interest-based statistical analysis and voxel-based statistical parametric mapping were performed. Both [11C]UCB-J ex vivo autoradiography and [3H]UCB-J in vitro autoradiography were used for the validation of the µPET data. Results At the age of 3 months, Sapap3 ko mice are already characterized by a significantly lower SV2A availability compared to wt littermates (i.a. cortex − 12.69%, p < 0.01; striatum − 14.12%, p < 0.001, thalamus − 13.11%, p < 0.001, and hippocampus − 12.99%, p < 0.001). Healthy ageing in control mice was associated with a diffuse and significant (p < 0.001) decline throughout the brain, whereas in Sapap3 ko mice this decline was more confined to the corticostriatal level. A strong linear relationship (p < 0.0001) was established between the outcome parameters of [11C]UCB-J µPET and [11C]UCB-J ex vivo autoradiography, while such relationship was absent for [3H]UCB-J in vitro autoradiography. Conclusions [11C]UCB-J PET is a potential marker for synaptic density deficits in the Sapap3 ko mouse model for OCD, parallel to disease progression. Our data suggest that [11C]UCB-J ex vivo autoradiography is a suitable proxy for [11C]UCB-J PET data in mice.

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RETRACTED ARTICLE: Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism

Cited by 11 publications

References 80 publications

Effects of Bergen 4-Day Treatment on Resting-State Graph Features in Obsessive-Compulsive Disorder

Effects of Bergen 4-Day Treatment on Resting-State Graph Features in Obsessive-Compulsive Disorder

Genetic and epigenetic architecture of Obsessive-Compulsive Disorder: In search of possible diagnostic and prognostic biomarkers

Sapap3 deletion causes dynamic synaptic density abnormalities: a longitudinal [11C]UCB-J PET study in a model of obsessive–compulsive disorder-like behaviour

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