Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat

摘要: Abstract The trophism of brain-derived neurotrophic factor (BDNF) for dopaminergic cells in culture has led to significant interest the role BDNF etiology and potential treatment Parkinson disease. Previous vivo investigation delivery axotomized substantia nigra neurons adult rat shown no protective effect. In this study, we produced nigral degeneration by infusing 1-methyl-4-phenylpyridinium (MPP+), a mitochondrial complex I inhibitor active metabolite 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), into striatum. The subsequent loss was presumably due toxicity after MPP+ uptake retrograde transport nigra. We engineered immortalized fibroblasts secrete human implanted these near 7 days before striatal infusion. found that BDNF-secreting markedly increased neuronal survival when compared control fibroblast implants. observation prevents MPTP-induced brain significance neurodegenerative disorders, which may involve dysfunction, such as