ABSTRACT
Polyethylenimine [PEI] has been proposed as a non-viral vector, and has been successfully used to transfer reporter genes into the central nervous system [CNS], kidneys, and lungs of adult mice. Neuropeptide Y [NPY] is a peptide expressed in the hypothalamus and is important in the regulation of body weight. Using PEI combined with stereotactic microinjection, we have successfully transferred cDNA-encoding NPY driven by the cytomegalovirus [CMV] promoter into the arcuate nucleus of adult male Wistar rats. Animals treated with NPY expressing plasmids [pNPY] gained more weight than the controls [p<0.05], with associated increases in food intake [p<0.05] and decreased brown adipose tissue activity, measured by Guanosine Diphosphate [GDP] binding to mitochondria, [p<0.05]. In a separate study, hypothalamic slices from the rats treated with pNPY/PEI showed increased NPY release [pNPY 9.7 +/- 0.3 fmol/l vs. control 8.3 +/- 0.5 fmol/l, p<0.05, n = 3]. These results suggest that PEI is an effective vector for gene transfer into the rodent brain and can increase the protein production sufficient to result a persistent phenotypic change. This technique offers the potential of a simple and effective method to manipulate gene expression localised to specific regions of the adult rodent brain