Title:Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets
Volume: 14
Issue: 7
Author(s): Ji-chun Zhang, Wei Yao and Kenji Hashimoto
Affiliation:
Keywords:
Brain-derived neurotrophic factor (BDNF), Depression, Hippocampus, Inflammation, Nucleus accumbens,
Prefrontal cortex, TrkB.
Abstract: Depression is the most prevalent and among the most debilitating of
psychiatric disorders. The precise neurobiology of this illness is unknown. Several lines
of evidence suggest that peripheral and central inflammation plays a role in depressive
symptoms, and that anti-inflammatory drugs can improve depressive symptoms in
patients with inflammation-related depression. Signaling via brain-derived neurotrophic
factor (BDNF) and its receptor, tropomycin receptor kinase B (TrkB) plays a key role in
the pathophysiology of depression and in the therapeutic mechanisms of
antidepressants. A recent paper showed that lipopolysaccharide (LPS)-induced
inflammation gave rise to depression-like phenotype by altering BDNF-TrkB signaling
in the prefrontal cortex, hippocampus, and nucleus accumbens, areas thought to be
involved in the antidepressant effects of TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) and TrkB
antagonist, ANA-12. Here we provide an overview of the tryptophan-kynurenine pathway and BDNF-TrkB
signaling in the pathophysiology of inflammation-induced depression, and propose mechanistic actions for
potential therapeutic agents. Additionally, the authors discuss the putative role of TrkB agonists and
antagonists as novel therapeutic drugs for inflammation-related depression.