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

被引：40

作者：

Arregui, Leticia ^{[1
,2
]}

Benitez, Jorge A. ^{[1
]}

Razgado, Luis F. ^{[1
]}

Vergara, Paula ^{[1
]}

Segovia, Jose ^{[1
]}

机构：

[1] IPN, Dept Fisiol Biofis & Neurociencias, Ctr Invest & Estudios Avanzados, Mexico City 07360, DF, Mexico

[2] Univ Autonoma Metropolitana Cuajimalpa, DCNI, Dept Ciencias Nat, Mexico City 11850, DF, Mexico

来源：

CELLULAR AND MOLECULAR NEUROBIOLOGY | 2011年 / 31卷 / 08期

关键词：

Brain-derived neurotrophic factor; Huntington's disease; Glial fibrillary acidic protein promoter; Adenovirus; Gene therapy; TYROSINE-HYDROXYLASE TRANSGENE; NEUROTROPHIC FACTOR; MOUSE MODEL; NEURODEGENERATIVE DISEASES; NEUROLOGICAL PHENOTYPE; NEURONAL DEGENERATION; BEHAVIORAL DEFICITS; GABAERGIC NEURONS; SPINY NEURONS; GENE-THERAPY;

D O I：

10.1007/s10571-011-9725-y

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：1229 / 1243

页数：15

共 69 条

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High potassium enhances secretion of neurotrophic factors from cultured astrocytes [J].