MON-722 Cross-Species Glucocorticoid-Sensitive Posterior Dentate Gyrus Gene Network: Developing a Polygenic Score Associated to Susceptibility to Depression After Early Life Adversity Exposure in Humans
| Autor: | Zihan Wang, Euclides José de Mendonça Filho, Randriely Merscher Sobreira de Lima, Irina Pokhvisneva, Sachin Patel, Danusa Mar Arcego, Michael J. Meaney, Barbara Barth, Jan-Paul Buschdorf, Nirmala Arul Rayan, Nick O’Toole, Patrícia Pelufo Silveira, Carla Dalmaz |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
business.industry Endocrinology Diabetes and Metabolism Dentate gyrus Gene regulatory network Early life Genetics and Development (including Gene Regulation) Endocrinology Internal medicine Genetics and Development and Non-Steroid Hormone Signaling II medicine business Glucocorticoid Depression (differential diagnoses) AcademicSubjects/MED00250 medicine.drug |
| Zdroj: | Journal of the Endocrine Society |
| ISSN: | 2472-1972 |
| Popis: | Exposure to stress during the life-course has consistently been associated with neuropsychological disorders, but the precise role of stress released glucocorticoids remains unclear in this context. We aimed at using hippocampal gene expression data from macaques to identify clusters of genes sensible to glucocorticoid exposure and create a biologically relevant polygenic score to investigate emotional disorders in a child and adult humans exposed to early adversity. RNA-sequencing data from the posterior dentate gyrus (pDG) of adult Macaca fascicularis females treated with Betamethasone (glucocorticoid) or saline injections for 8 consecutive days were analyzed from two cohorts: Singapore (reference) and Vietnam (replication) with N=12/each. Weighted gene co-expression network analysis (WGCNA) was used to identify clusters (modules) of co-expressed genes associated with betamethasone. In Singaporean animals, genes were clustered in 52 modules, in which 5 were associated with betamethasone. Two modules were preserved in a replication dataset (Vietnam) and in data from female rats treated with corticosterone for 6 weeks, being the black module (557 genes, P=0.01, r=0.7) the one having the highest correlation with glucocorticoid exposure. Gene ontology analysis (FDR |
| Databáze: | OpenAIRE |
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