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), neurotrop hin-3 (NT-3), neurotrophin 4/5 (NT-4/5) and nerve growth factor (NGF), were compared for their effects on the survival and differentiation o f embryonic rat striatal neurons grown in low-density cultures. Treatm ent with BDNF for 8 days resulted in a 40% increase in overall neurona l survival, a 3- to 5-fold increase in the number of calbindin-immunor eactive neurons, and an 80% increase in GABA-positive neurons. Treatme nt 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 nu mber similar to that induced by BDNF. BDNF treatment produced a striki ng morphological differentiation of striatal GABAergic neurons, which was characterized by a doubling of the number of neurite branch points , the total area of arborization and the perikaryal area compared to c ontrol cultures, All three of these factors increased high-affinity GA BA 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,