Egr3 immediate early gene and the brain-derived neurotrophic factor in bipolar disorder

Bianca Pfaffenseller, Flavio Kapczinski, Amelia L Gallitano-Mendel, Fábio Klamt

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number15
JournalFrontiers in Behavioral Neuroscience
Volume12
DOIs
StatePublished - Feb 5 2018

Fingerprint

Immediate-Early Genes
Brain-Derived Neurotrophic Factor
Bipolar Disorder
Genes
Growth
Early Growth Response Protein 3
Psychiatry
Nerve Growth Factor Receptors
Neuronal Plasticity
Gene Regulatory Networks
Brain
Prefrontal Cortex
Cognition
Veins
Intercellular Signaling Peptides and Proteins
Gene Expression

Keywords

  • Bipolar disorder
  • Brain-derived neurotrophic factor (BDNF)
  • Early growth response gene 3 (EGR3)
  • Immediate early genes
  • Neuroplasticity
  • Regulatory network

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Cite this

Egr3 immediate early gene and the brain-derived neurotrophic factor in bipolar disorder. / Pfaffenseller, Bianca; Kapczinski, Flavio; Gallitano-Mendel, Amelia L; Klamt, Fábio.

In: Frontiers in Behavioral Neuroscience, Vol. 12, 15, 05.02.2018.

Research output: Contribution to journalArticle

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