A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression

• Main Authors: Chen C, Dong Y, Liu F, Gao C, Ji C, Dang Y, Ma X, Liu Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-03-01
• Series: Neuropsychiatric Disease and Treatment
• Subjects: post stroke depression (psd); bdnf-ha2tat/aav; nasal-brain pathway; hippocampus; prefrontal cortex;
• Online Access: https://www.dovepress.com/a-study-of-antidepressant-effect-and-mechanism-on-intranasal-delivery--peer-reviewed-article-NDT

Ce Chen,1,* Yingying Dong,1,* Fei Liu,2 Chengge Gao,1 Cui Ji,3 Yonghui Dang,4 Xiancang Ma,1 Yong Liu5 1Department of Psychiatry, First Affiliated Hospital of Medical College Xi’an Jiaotong University, Xi’an 710061, Shaanxi, People’s Republic of China; 2Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xi’an Jiaotong University, Xi’an 710004, Shaanxi, People’s Republic of China; 3The Hospital of Xidian University, Xi’an 710071, Shaanxi, People’s Republic of China; 4College of Medicine & Forensics, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi, People’s Republic of China; 5The Institute of Neurobiology, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong LiuThe Institute of Neurobiology, Xi’an Jiaotong University, Yanta Road W. 76#, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel [phone]Email [e-mail]: Post-stroke depression (PSD) is one of the most frequent neuropsychiatric disorders associated with stroke characterized by depression. The neuroplasticity hypothesis postulates that loss of brain-derived neurotrophic factor (BDNF) plays a major role in pathophysiology of PSD, and restoration of it may represent a critical mechanism underlying antidepressant efficacy.Methods: In previous studies, we designed a new fusion gene, HA2TAT-BDNF, and cloned it into adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for the delivery of BDNF to central nervous system (CNS) via nose-brain pathway. In this study, we used it to explore the antidepressant effects on PSD rats through behavioral and various histological methods, and try to find out its specific mechanism.Results: Compared with the control group, the PSD+AAV group showed decreased sucrose consumption percentage in the sucrose preference test (SPT) (P < 0.001) and prolonged immobility in the forced swimming test (FST) (P=0.000). However, the nasal administration of BDNF-HA2TAT/AAV reversed results of these two behavioral tests (P> 0.05, P > 0.05), showing an adequate antidepressant effect. Compared with the control group, the concentrations of BDNF mRNA and protein in the hippocampus (P< 0.05, P < 0.01) and prefrontal cortex (P < 0.01, P < 0.01) of PSD rats both decreased. Increased BDNF mRNA and protein expression was observed in the prefrontal cortex (P > 0.05, P < 0.05), without notable change in the hippocampus (P < 0.05, P < 0.001) of PSD+BDNF rats.Conclusion: These results suggest that BDNF reductions in the prefrontal cortex and hippocampus are associated with the development of post-stroke depression, and that increased levels of BDNF in the prefrontal cortex could be used as a therapeutic target to treat PSD. However, the exact mechanism of BDNF action remains unclear in this regard, hindering the wider application of our method. We expect that our research could facilitate the exploration of pathogenesis and the new treatment method of PSD.Keywords: post-stroke depression, PSD, BDNF-HA2TAT/AAV, nasal-brain pathway, hippocampus, prefrontal cortex