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Lipid-Mediated In Vivo Gene Transfer Replaces the Loss of Choline Acetyltransferase Activity After Unilateral Fimbria-Fornix Aspiration

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Abstract:

In Alzheimer's disease cholinergic neurons degenerate, resulting in loss of hippocampal acetylcholine. The fimbria-fornix aspiration is a well-known animal model mimicking hippocampal cholinergic deficiency. The aim of the present study was to use in vivo lipid-mediated gene transfer to introduce an expression vector coding for the acetylcholine synthesizing enzyme choline acetyltransferase into the hippocampus to replace the loss of enzyme activity after unilateral fimbria-fornix aspiration. Our data show that the lipid FuGene is useful to transfer DNA in vitro into 3T3 fibroblasts, C6 glioma cells, and primary astroglia and to express the respective enzyme. Lipid-mediated gene transfer in vivo resulted in a marked but transient expression of green fluorescent protein below the injection site peaking 5 days after the injection. Unilateral fimbria-fornix aspiration led to a marked reduction in the activity of choline acetyltransferase in the hippocampus, which was completely replaced 5 days after lipid-mediated gene transfer of the choline acetyltransferase vector. In conclusion, our data provide evidence that lipid-mediated gene transfer using FuGene is a useful tool to replace loss of choline acetyltranseferase activity in the hippocampus after fimbria-fornix aspiration; however, the lack of good gene transfer efficiency and the transient nature of expression limit its use for clinical applications.

Keywords: FuGene; Nonviral; Gene therapy; Key words: Acetylcholine; Alzheimer’s disease; Choline acetyltransferase

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000001783986233

Affiliations: Laboratory of Psychiatry, Clinic of Psychiatry, University Hospital Innsbruck, Austria

Publication date: August 1, 2001

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
cog/ct/2001/00000010/00000008/ct261
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