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

Xiao-Ling Li,1,* Hua Liu,2,* Shu-Han Liu,2 Yong Cheng,2,3 Guo-Jun Xie1 1The Third People’s Hospital of Foshan, Foshan, People’s Republic of China; 2Center on Translational Neuroscience, School of Pharmacy, Minzu University of China, Beijing, People’s Republic of China; 3Institute of National Security, Minzu University of China, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Cheng, Minzu Unviersity of China, 27 South Zhongguancun Avenue, Beijing, 100081, People’s Republic of China, Email yongcheng@muc.edu.cn Guo-Jun Xie, The Third People’s Hospital of Foshan, 102 South Jinlan Road, Foshan, 528041, People’s Republic of China, Email xiegjfs@163.comIntroduction: 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