期刊
CELLULAR AND MOLECULAR NEUROBIOLOGY
卷 31, 期 8, 页码 1229-1243出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-011-9725-y
关键词
Brain-derived neurotrophic factor; Huntington's disease; Glial fibrillary acidic protein promoter; Adenovirus; Gene therapy
资金
- Conacyt [42721-M, 54756]
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.
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