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Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis

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Author(s):
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Lisboa, Bianca C. G. ; Oliveira, Katia C. ; Tahira, Ana Carolina ; Barbosa, Andre Rocha ; Feltrin, Arthur Sant'Anna ; Gouveia, Gisele ; Lima, Luzia ; Feio dos Santos, Ana Cecilia ; Martins Jr, David Correa ; Puga, Renato David ; Moretto, Ariane Cristine ; De Braganca Pereira, Carlos Alberto ; Lafer, Beny ; Paraizo Leite, Renata Elaine ; De Lucena Ferretti-Rebustini, Renata Eloah ; Farfel, Jose Marcelo ; Grinberg, Lea Tenenholz ; Jacob-Filho, Wilson ; Miguel, Euripedes Constantino ; Hoexter Helena Brentani, Marcelo Queiroz ; Brentani, Helena
Total Authors: 21
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, p. 12-pg., 2019-02-28.
Abstract

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD. (AU)

FAPESP's process: 15/01587-0 - Storage, modeling and analysis of dynamical systems for e-Science applications
Grantee:João Eduardo Ferreira
Support Opportunities: Research Grants - eScience and Data Science Program - Thematic Grants