Abstract
Major depressive disorder (MDD) is a debilitating and widespread illness that exerts significant personal and socioeconomic consequences. Recent genetic and brain-imaging studies suggest that bicaudal C homolog 1 gene (BICC1), which codes for an RNA-binding protein, may be associated with depression. Here, we show that BICC1 mRNA is upregulated in the dorsolateral prefrontal cortex and dentate gyrus of human postmortem MDD patients. We also show that BICC1 is increased in the prefrontal cortex and hippocampus in the rat chronic unpredictable stress (CUS) model of depression. In addition, we show in vivo that a single acute antidepressant dose of ketamine leads to a rapid decrease of BICC1 mRNA, while in vitro, we show that this is likely due to neuronal activity-induced downregulation of BICC1. Finally, we show that BICC1 knockdown in the hippocampus protects rats from CUS-induced anhedonia. Taken together, these findings identify a role for increased levels of BICC1 in the pathophysiology of depressive behavior.
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Acknowledgements
We are grateful to the families consenting to donate brain tissue and be interviewed for the human tissue samples, and to the Cuyahoga County Medical Examiner’s Office for their assistance. We thank Dr Grazyna Rajkowska for identification of anatomically comparable regions of dlPFC and Dr Vanja Duric for technical assistance with preparation of the postmortem samples. We thank Dr Mounira Banasr and Ashley Lepack for preparation of primary neuronal cultures and for technical assistance with the fluoxetine-treated rat samples. We also thank Dr Ralph J DiLeone for providing us with the pAAV-GFP-shRNA backbone plasmid.
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Ota, K., Andres, W., Lewis, D. et al. BICC1 Expression is Elevated in Depressed Subjects and Contributes to Depressive Behavior in Rodents. Neuropsychopharmacol 40, 711–718 (2015). https://doi.org/10.1038/npp.2014.227
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DOI: https://doi.org/10.1038/npp.2014.227
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