Antidepressant effect of recombinant NT4-NAP/AAV on social isolated mice through intranasal route

// Fei Liu 1, 2, * , You-ping Liu 1, 3, * , Gang Lei 1 , Peng Liu 1 , Zheng Chu 1 , Cheng-ge Gao 4 , Yong-hui Dang 1, 5, 6 1 College of Medicine & Forensics, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, PR China 2 Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710004, PR China 3 Sun Yat-sen University Cancer Center, Guangzhou, 510060, PR China 4 Department of Psychiatry, First Affiliated Hospital of Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, PR China 5 Key Laboratory of the Health Ministry for Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, PR China 6 Key Laboratory of Forensic Medicine of Shaanxi Province, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, PR China * These authors have contributed equally to this work Correspondence to: Yong-hui Dang, email: psydyh@mail.xjtu.edu.cn Keywords: social isolation, depression, NT4-NAP/AAV, intranasal administration, antidepressant Received: October 09, 2016 Accepted: December 13, 2016 Published: December 29, 2016 ABSTRACT The purpose of the present study was to observe the depression-like behavior induced by social isolation; detect the antidepressant effect of a recombinant adeno-associated virus (AAV) expressing NAP on social isolation mice by intranasal delivery. After construction of NT4-NAP/AAV, expression of NAP was confirmed in vitro . 3-week-old C57/BL mice were bred individually in cages as social isolation-rearing. Six weeks later, the first subset of mice underwent behavioral tests and western blot; the second was for enzyme-linked immunosorbent assay. NT4-NAP/AAV was delivered quaque die by nasal administration for consecutive 10 days before behavioral test. Several depression-like behaviors were observed in social isolation mice, including decreased relative sucrose preference, longer immobility time in forced swimming test, lower plasma corticosterone and decreased brain-derived neurotrophic factor in hippocampus. Thus, social isolation procedure appears to be an animal model of depression with good face and construct validity. What’s more, the antidepressant effect in social isolation-rearing mice was observed after intranasal administration of NT4-NAP/AAV, suggesting that this might be a promising therapeutic strategy for depressive disorder.