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Cellular and Molecular Neurobiology

, Volume 31, Issue 8, pp 1229–1243 | Cite as

Adenoviral Astrocyte-Specific Expression of BDNF in the Striata of Mice Transgenic for Huntington’s Disease Delays the Onset of the Motor Phenotype

  • Leticia Arregui
  • Jorge A. Benítez
  • Luis F. Razgado
  • Paula Vergara
  • Jose SegoviaEmail author
Original Research

Abstract

Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. The most characteristic structural feature of this disease is neurodegeneration accompanied by gliosis in the striatum. BDNF has been proposed to protect striatal neurons from degeneration, because it is an important survival factor for these neurons from development to adulthood. Considering the extensive gliosis and the survival effects of BDNF, we constructed an adenovirus to express a BDNF cDNA in astrocyte cells using a promoter of the glial fibrillary acidic protein gene. Cells stably transfected in vitro with a BDNF cDNA driven by this promoter expressed BDNF and responded to external stimuli increasing BDNF production. When the vector was applied into the striata of mice transgenic for HD, long-term expression of the transgene was observed, associated with a delay of onset of the motor phenotype of the R6/2 HD transgenic mice. The present data indicate that the striatal expression of BDNF is a potential adjuvant for the treatment of HD.

Keywords

Brain-derived neurotrophic factor Huntington’s disease Glial fibrillary acidic protein promoter Adenovirus Gene therapy 

Notes

Acknowledgments

We want to thank Dr. M. Mouradian for the kind gift of the BDNF cDNA, Dr. B. Vogelstein (Johns Hopkins University) for providing us with the reagents (pAdSystem) to construct the adenoviral vectors, and Dr. M. Hernández (Cinvestav) for providing us with the antibody against β-actin. We thank R. Sánchez for technical support. This work was partially supported by Conacyt Grants 42721-M and 54756 (JS).

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Leticia Arregui
    • 1
    • 2
  • Jorge A. Benítez
    • 1
    • 3
  • Luis F. Razgado
    • 1
  • Paula Vergara
    • 1
  • Jose Segovia
    • 1
    Email author
  1. 1.Departamento de Fisiología, Biofísica y NeurocienciasCentro de Investigación y de Estudios Avanzados del IPNMexicoMexico
  2. 2.Departamento de Ciencias Naturales, DCNIUniversidad Autónoma Metropolitana CuajimalpaMexicoMexico
  3. 3.Ludwig Institute for Cancer ResearchUniversity of CaliforniaSan DiegoUSA

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