Influence of BDNF on the expression of the dopaminergic phenotype of tissue used for brain transplants
Abstract
Brain-derived neurotrophic factor (BDNF) has previously been shown by this laboratory among others to promote survival and differentiation of central dopaminergic neurons and to stimulate expression of the dopaminergic phenotype in fetal cerebrocortex in vitro. We have examined the effect of BDNF antibody on nigral dopaminergic neurons in vivo and in vitro. It reduced the survival of rat fetal dopaminergic neurons in culture (up to 40% died). The BDNF antibody also caused ipsilateral rotation after a single in vivo intranigral injection in the adult rats. Pre-treatment of fetal nigral neurons with BDNF improved the performance of dopaminergic cells in fetal nigral transplants based on surviving TH+ cells numbers. Thus, parkinsonian rats receiving fetal nigral cells treated with BDNF showed a significantly greater reduction of turning over the 3 weeks following transplantation, compared with the rats receiving untreated nigral transplants. However, the average number of tyrosine hydroxylase (TH)-positive neurons in the grafts of rats receiving fetal nigral cells treated with BDNF was 211 +/- 35 which was only about 20% of the cell number (1012 +/- 223, mean +/- S.E.M.) found in those receiving untreated nigral transplants. These...Continue Reading
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