title: Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder.
abstract: Depression is a disturbing psychiatric disease with unsatisfied therapy. Not all patients are sensitive to anti-depressants currently in use, side-effects are unavoidable during therapy, and the cases with effectiveness are always accompanied with delayed onset of clinical efficacy. Delivering brain-derived neurotrophic factor (BDNF) to brain seems to be a promising therapy. However, a better approach to delivery is still rudimentary. The purpose of our present work is to look for a rapid-onset and long-lasting therapeutic strategy for major depressive disorder (MDD) by effectively delivering BDNF to brain. BDNF, fused with cell-penetrating peptides (TAT and HA2), was packaged in adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for intranasally delivering BDNF to central nervous system (CNS) via nose-brain pathway. Intranasal administration of BDNF-HA2TAT/AAV to normal mice displayed anti-depression effect in forced swimming test when the delivery lasted relatively longer. The AAV applied to mice subjected to chronic mild stress (CMS) through intranasal administration for 10 days also alleviated depression-like behaviors. Western-blotting analysis revealed that BDNF-HA2TAT/AAV nasal administration enhanced hippocampal BDNF content. These results indicate intranasal administration of constructed BDNF-HA2TAT/AAV exerts anti-depression effect in CMS mice by increasing hippocampal BDNF, suggesting that this strategy holds a promising therapeutic potential for MDD.
authors.affiliation: Department of Psychiatry, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Xian-cang
authors.initials: XC
authors.lastname: Ma
authors.affiliation: College of Medicine &Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of CT/MRI, Shaanxi Provincial People's Hospital, Xi'an, China.
authors.forename: Xiao-ling
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Wen-hui
authors.initials: WH
authors.lastname: Jiang
authors.affiliation: Department of Psychiatry, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Xi'an Ankang Hospital, Xi'an, China.
authors.forename: Cai-xia
authors.initials: CX
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Ying-ying
authors.initials: YY
authors.lastname: Dong
authors.affiliation: College of Medicine &Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, China.|Key Laboratory of the Health Ministry for Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, China.|Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Yong-hui
authors.initials: YH
authors.lastname: Dang
authors.affiliation: Department of Psychiatry, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Cheng-ge
authors.initials: CG
authors.lastname: Gao
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D057846:Cell-Penetrating Peptides / Q000096:biosynthesis / Q000235:genetics; D000229:Dependovirus; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D057846:Cell-Penetrating Peptides; D011993:Recombinant Fusion Proteins; C579455:BDNF protein, human