Fig. 6.

Effects of glutamate receptor antagonists and NMDA after 24 hr exposure. Striatal cultures of 1 DIV were exposed to different ionotropic glutamate receptor antagonists, NMDA, or vehicle control. a, Treatment duration was 24 hr and was followed by 2 hr exposure to BrdU (20 μg/ml) and fixation in PFA (diagram). Treatment with MK-801 or CGS 19755 significantly reduced the proportion of nuclei incorporating BrdU with respect to control cultures. Effect of the competitive antagonist (CGS) could be countered by addition of NMDA. Addition of 100 μm NMDA to CGS-treated cultures restored BrdU uptake close to normal levels. Exposure to NBQX did not alter BrdU uptake, suggesting that NMDA but not AMPA receptor blockade results in decreased proliferation. In cultures in which only the agonist was added, BrdU uptake was inversely proportional to NMDA concentration. At 1 μm, NMDA significantly upregulated proliferation, whereas increasing doses exhibited toxic effects. B, The proportion of Tuj1-positive cells were also quantified after each treatment. Exposure to MK-801 or CGS 19755 reduced the proportion of TUJ1 cells, suggesting that production of early postmitotic neurons was reduced after receptor blockade. Tuj1 cell number also decreased after treatment with 100 μm NMDA. c, MAP2+ cell number did not alter significantly after treatment, with the exception of NMDA at excitotoxic concentrations, suggesting that the short-term survival of more mature neurons was not affected by the agents added. Data expressed as mean ± SEM (n = 3; *p < 0.01 vs control).