Intranasal Administration of Brain-Derived Neurotrophic Factor Rescues Depressive-Like Phenotypes in Chronic Unpredictable Mild Stress Mice

Introduction: Major depression disorder is the most common diagnosed mental illnesses, and it bring a high social and economic burden. However, the current treatment for depression has limitations with side effects. Hence, there is an urgent need to search more effective treatment for major depressive disorder. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons.Methods: We administered BDNF into chronic unpredictable mild stress (CUMS)-induced depression mice and assessed the effects of intranasal delivery of BDNF in depression by the tail suspension test, forced swimming test, novelty suppressed feeding test, and open-field test.Results: We find that the intranasal administration of BDNF reversed the depressive-like behaviors in CUMS mice as measured Further analyses suggested that BDNF treatment reduced pro-inflammatory cytokine (IL-6, TNF-alpha, iNOS and IL-1 beta) expressions in the hippocampus of CUMS mice. In addition, our results showed that BDNF markedly reduced oxidative stress in the hippocampus and blood of CUMS mice. Moreover, our data suggested that BDNF treatment increased neurogenesis in the hippocampus of CUMS mice.Discussion: Taken together, our results for the first time demonstrated that intranasal delivery of BDNF protein exhibited anti-depressant-like effects in mice, and therefore may represent a new therapeutic strategy for major depressive disorder.

Automated summary

This study demonstrates that intranasal administration of BDNF can reduce depressive-like behaviors induced by chronic unpredictable mild stress, decrease the expression of inflammatory cytokines, and attenuate oxidative stress. Additionally, BDNF treatment increases neurogenesis in the hippocampus. These findings suggest that BDNF may represent a new therapeutic strategy for major depressive disorder.