Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons

摘要: Brain derived neurotrophic factor (BDNF) expression is significantly reduced in the Parkinson's disease substantia nigra. This neurotrophin has potent affects on dopaminergic neuron survival protecting them from neurotoxins MPTP and 6-hydroxydopamine (6-OHDA) commonly used to create animal models of also promoting axonal sprouting. In this study, we demonstrate that an antisense oligonucleotide infusion (200 nM for 28 days) prevent BDNF production nigra rats mimics many features classical disease. 62% treated rotate (P < or = 0.05) response receptor stimulation by apomorphine. 40% pars compacta tyrosine hydroxylase immunoreactive neurons are lost 0.00001) dopamine uptake site density measured (3)H-mazindol autoradiography 34% 0.005). Loss haematoxylin eosin stained nigral significant 0.0001) but less extensive (34%). These observations indicate loss leads both down regulation phenotype neuronal death. Therefore, mRNA may contribute directly death development