Mice with altered BDNF signaling as models for mood disorders and antidepressant effects.

Jesse S O Lindholm,Eero Castrã©N

doi:10.3389/fnbeh.2014.00143

Abstract

Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB support neuronal survival during development and promote connectivity and plasticity in the adult brain. Decreased BDNF signaling is associated with the pathophysiology of depression and the mechanisms underlying the actions of antidepressant drugs (AD). Several transgenic mouse models with decreases or increases in the amount of BDNF or the activity of TrkB signaling have been created. This review summarizes the studies where various mouse models with increased or decreased BDNF levels or TrkB signaling were used to evaluate the role of BDNF signaling in depression-like behavior. Although a large number of models have been employed and several studies have been published, no clear-cut connections between BDNF levels or signaling and depression-like behavior in mice have emerged. However, it is clear that BDNF plays a critical role in the mechanisms underlying the actions of AD.

Highlights

Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB support neuronal survival during development and promote connectivity and plasticity in the adult brain
Impaired BDNF signaling through TrkB is associated with the pathophysiology of mood disorders and neuronal plasticity promoted by BDNF underlies some of the actions of antidepressant drugs (AD) (Duman and Monteggia, 2006; Castrén et al, 2007)
BDNF deficient mice are the most used model for these studies. These models have demonstrated a key role for BDNFTrkB signaling in the mechanisms underlying the actions of ADs (MacQueen et al, 2001; Saarelainen et al, 2003; Chourbaji et al, 2004; Ibarguen-Vargas et al, 2009; Lindholm et al, 2012)

Summary

Introduction

Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB support neuronal survival during development and promote connectivity and plasticity in the adult brain. BDNF(±) mice do not show any clear baseline anxiety- or depression-like behaviors, but they are more vulnerable to stress and the effects of ADs are blocked in these mice. Depression-like behavior after stress or MEK inhibitor Increased anxiety-like behavior, no changes in locomotor activity No behavioral changes, increased weight Impaired learning and memory No behavioral changes, effects of ADs blocked in heterozygous mice

Results

Conclusion