PMID- 29459824 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1662-5153 (Print) IS - 1662-5153 (Electronic) IS - 1662-5153 (Linking) VI - 12 DP - 2018 TI - EGR3 Immediate Early Gene and the Brain-Derived Neurotrophic Factor in Bipolar Disorder. PG - 15 LID - 10.3389/fnbeh.2018.00015 [doi] LID - 15 AB - Bipolar disorder (BD) is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs) are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 (EGR3) of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients. As a central transcription factor, EGR3 regulates an array of target genes that mediate critical neurobiological processes such as synaptic plasticity, memory and cognition. Considering that EGR3 expression is induced by brain-derived neurotrophic factor (BDNF) that has been consistently related to BD pathophysiology, we suggest a link between BDNF and EGR3 and their potential role in BD. A growing body of data from our group and others has shown that peripheral BDNF levels are reduced during mood episodes and also with illness progression. In this same vein, BDNF has been proposed as an important growth factor in the impaired cellular resilience related to BD. Taken together with the fact that EGR3 regulates the expression of the neurotrophin receptor p75NTR and may also indirectly induce BDNF expression, here we propose a feed-forward gene regulatory network involving EGR3 and BDNF and its potential role in BD. FAU - Pfaffenseller, Bianca AU - Pfaffenseller B AD - Laboratory of Molecular Psychiatry, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Kapczinski, Flavio AU - Kapczinski F AD - Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada. FAU - Gallitano, Amelia L AU - Gallitano AL AD - Department of Basic Medical Sciences, College of Medicine, University of Arizona, Phoenix, AZ, United States. FAU - Klamt, Fabio AU - Klamt F AD - Laboratory of Cellular Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. LA - eng GR - R01 MH097803/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20180205 PL - Switzerland TA - Front Behav Neurosci JT - Frontiers in behavioral neuroscience JID - 101477952 PMC - PMC5807664 OTO - NOTNLM OT - bipolar disorder OT - brain-derived neurotrophic factor (BDNF) OT - early growth response gene 3 (EGR3) OT - immediate early genes OT - neuroplasticity OT - regulatory network EDAT- 2018/02/21 06:00 MHDA- 2018/02/21 06:01 PMCR- 2018/01/01 CRDT- 2018/02/21 06:00 PHST- 2017/06/21 00:00 [received] PHST- 2018/01/17 00:00 [accepted] PHST- 2018/02/21 06:00 [entrez] PHST- 2018/02/21 06:00 [pubmed] PHST- 2018/02/21 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fnbeh.2018.00015 [doi] PST - epublish SO - Front Behav Neurosci. 2018 Feb 5;12:15. doi: 10.3389/fnbeh.2018.00015. eCollection 2018.