Open AccessPromotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3.
Author(s) -
Beat Knüsel,
John Winslow,
Ar Rosenthal,
Louis E. Burton,
Derice P. Seid,
Károly Nikolics,
Franz Hefti
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.3.961
Subject(s) - cholinergic neuron , nerve growth factor , basal forebrain , cholinergic , dopaminergic , neurotrophic factors , neurotrophin , biology , glial cell line derived neurotrophic factor , neurotrophin 3 , medicine , neuroscience , endocrinology , brain derived neurotrophic factor , dopamine , receptor , biochemistry
Recombinant human brain-derived neurotrophic factor (rhBDNF) and neurotrophin 3 (rhNT-3), two recently cloned molecules closely related to nerve growth factor (NGF), were produced from human cDNA expressed in human embryonic kidney cells. The recombinant proteins were tested in cultures of dissociated fetal rat brain cells containing basal forebrain cholinergic neurons. rhBDNF stimulated the differentiation of the cholinergic neurons, similar to NGF, which is well established as a neurotrophic factor for these cells. However, rhBDNF was particularly effective during the first few days in vitro, whereas the stimulatory action of rhNGF was more pronounced later in the development of the cultures. This finding indicates the existence of different time periods of responsiveness of the cholinergic neurons to BDNF and NGF. To assess the selectivity of the effect of rhBDNF on cholinergic neurons, its actions were tested in cultures of ventral mesencephalon containing dopaminergic cells. In contrast to NGF, which does not affect central dopaminergic neurons, rhBDNF increased dopamine uptake activity. The findings suggest that BDNF stimulates survival or differentiation of other cells besides the cholinergic neurons.