TROPHIC AND PROTECTIVE ACTIONS OF BRAIN-DERIVED NEUROTROPHIC FACTOR ON STRIATAL DARPP-32-CONTAINING NEURONS IN-VITRO

We have examined the effects of either brain-derived neurotrophic fact or (BDNF), the BB-isoform of platelet-derived growth factor (PDGF-BB), or a combination of these growth factors on the survival and the morp hological development of embryonic striatal neurons grown under serum- free culture conditions. Striatal neurons were identified using immuno cytochemistry for ''dopamine- and adenosine 3':5'-monophosphate-reguta ted phosphoprotein with a molecular weight of 32 kilodalton'' (DARPP-3 2). BDNF and PDGF-BB promoted the survival of DARPP-32-positive neuron s, with the magnitude of their effects bring comparable. A combination of these growth factors exerted no significant additive effects on ce ll survival. BDNF stimulated morphological differentiation of DARPP-32 -containing neurons by increasing the length of neurites, the number o f branching points on the neurites, and the soma area. By contrast, PD GF-BB increased the neurite length and the cell body area, but not the number of branching points. BDNF also protected striatal neurons from excitotoxicity induced by N-methyl-D-aspartate, whereas PDGF-BB had n o effect under the same treatment conditions as those for BDNF. Thus, BDNF is trophic for striatal DARPP-32-containing neurons in vitro by e nhancing the survival, morphological differentiation and resistance to excitotoxicity, and its mechanisms of action are probably different f rom those of PDGF-BB.