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

Abstract

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-α, iNOS and IL-1β) 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.

Keywords:

• depression
• BDNF
• neurogenesis
• inflammatory cytokine
• oxidative stress

Data Sharing Statement

All data are contained within the manuscript.

Acknowledgments

This study was supported by the Natural Science Foundation of Guangdong Province (2114050002827), the National Natural Science Foundation of China (82071676), the High-Level Hospital Development Program for Foshan “Climbing” Project, and Foshan Science and technology innovation project (2020001005608).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that there are no conflicts of interest.