The neurotrophins BDNF, NT-3 and NT-4/5 promote survival and morphological and biochemical differentiation of striatal neurons in vitro.
The neurotrophins, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin 4/5 (NT-4/5) and nerve growth factor (NGF), were compared for their effects on the survival and differentiation of embryonic rat striatal neurons grown in low-density cultures. Treatment with BDNF for 8 days resulted in a 40% increase in overall neuronal survival, a 3- to 5-fold increase in the number of calbindin-immunoreactive neurons, and an 80% increase in GABA-positive neurons. Treatment with NT-3 or NT-4/5 produced a 2- to 3-fold increase in the number of calbindin-positive neurons and an increase in GABA-positive cell number similar to that induced by BDNF, BDNF treatment produced a striking morphological differentiation of striatal GABAergic neurons, which was characterized by a doubling of the number of neurite branch points, the total area of aborization and the perikaryal area compared to control cultures. All three of these factors increased high-affinity GABA uptake 2-fold. NGF had no effect on any of the parameters examined. Our results show that BDNF, NT-3 and NT-4/5 promote the survival and/or differentiation of calbindin-immunopositive and GABAergic striatal neurons.
Ventimiglia
R
R
Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
Mather
P E
PE
Jones
B E
BE
Lindsay
R M
RM
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D064026:Calbindins; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D020933:Neurotrophin 3; D010641:Phenotype; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D064026:Calbindins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D064030:S100 Calcium Binding Protein G; C071951:neurotrophin 5; C073922:neurotrophin 4