title: Adenoviral astrocyte-specific expression of BDNF in the striata of mice transgenic for Huntington's disease delays the onset of the motor phenotype.
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.
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Av. Instituto Politécnico Nacional # 2508, 07360 Mexico, DF, Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Arregui
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Benítez
authors.forename: Luis F
authors.initials: LF
authors.lastname: Razgado
authors.forename: Paula
authors.initials: P
authors.lastname: Vergara
authors.forename: Jose
authors.initials: J
authors.lastname: Segovia
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D019076:Transgenes
chemical_list: D019208:Brain-Derived Neurotrophic Factor