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Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect

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Abstract

The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

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Acknowledgments

The project was supported by the National Science Foundation of China (No. 81171256 to Xian-Cang Ma, No. 81271487 to Cheng-ge Gao and No. 81270416 to Xiao-Ling Zhang).

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Authors and Affiliations

  1. Department of Psychiatry, First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, China

    Xian-Cang Ma, Wen-Hui Jiang, Min Jia & Cheng-Ge Gao

  2. College of Medicine and Forensics, Xi’an Jiaotong University Health Science Center, Xi’an, China

    Zheng Chu & Yong-Hui Dang

  3. Department of CT/MRI, Shaanxi Provincial People’s Hospital, Xi’an, China

    Xiao-Ling Zhang

  4. Key Laboratory of the Health Ministry for Forensic Medicine, Xi’an Jiaotong University Health Science Center, Xi’an, China

    Yong-Hui Dang

  5. Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, Xi’an Jiaotong University Health Science Center, Xi’an, China

    Yong-Hui Dang

Authors
  1. Xian-Cang Ma
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  2. Zheng Chu
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  3. Xiao-Ling Zhang
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  4. Wen-Hui Jiang
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  5. Min Jia
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  6. Yong-Hui Dang
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  7. Cheng-Ge Gao
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Correspondence to Yong-Hui Dang or Cheng-Ge Gao.

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Ma, XC., Chu, Z., Zhang, XL. et al. Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect. Neurochem Res 41, 1375–1380 (2016). https://doi.org/10.1007/s11064-016-1841-0

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  • DOI: https://doi.org/10.1007/s11064-016-1841-0

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