Recent studies have shown that administration of exogenous nerve growth factors (NGF) can attenuate cholinergic neuronal deficits and improve spatial memory in aged rats. Although administration of exogenous proteins has been proven behaviorally beneficial in aged rats, the limitations imposed by protein degradation and by the blood brain barrier restrict the clinical utility of these approaches. There is a need to develop long term delivery of therapeutic levels of neurotrophic factor into CNS for improvement of memory function following aging. The goal of this proposal is to study the therapeutic potential of cationic liposome-mediated neurotrophic gene transfection to improve the spatial memory in aged rats. These studies test the hypothesis that non- viral vector-mediated neurotrophic gene transfer can preserve the cholinergic system and improve spatial memory. We will apply newly developed cationic liposome-mediated gene transfer techniques to transfer NGF genes into the aged rat brain. We will optimize the cationic liposome-mediated gene transfection in aged rat brain by using a different route of injection to deliver cDNA-liposome complexes. Efficacy will be examined by cholinergic neurons and spatial memory after applying optimized delivery of neurotrophic cDNA-liposome complexes into the aged rat brain. The cholinergic system will be examined by ChAT immunohistochemical analysis. The spatial memory function will be evaluated by Morris water maze test. This study will minimally provide useful information for developing new strategies to improve the memory function in aged rats by using non- viral vector-mediated neurotrophic gene transfer.
| Zou, L; Yuan, X; Zhou, H et al. (2001) Helper-dependent adenoviral vector-mediated gene transfer in aged rat brain. Hum Gene Ther 12:181-91 |
| Zou, L; Zhou, H; Pastore, L et al. (2000) Prolonged transgene expression mediated by a helper-dependent adenoviral vector (hdAd) in the central nervous system. Mol Ther 2:105-13 |
