FIGURE 5.

NMDA-induced neurotoxicity in mature neuron is p38 MAPK pathway-dependent, whereas neuroprotection in immature neuron is ERK1/2-dependent. At 12 or 3DIV, neurons were pretreated with p38 MAPK-specific inhibitor SB203580 (10 μm), ERK1/2-specific inhibitor PD98059 (10 μm), or DMSO for 20 min followed by treatment with or without NMDA (100 μm) for 15 min in modified Locke's solution and washed three times with DMEM and then incubated with original culture medium (A–C) or DMEM (D and E). LDH release measurement and Hoechst staining were conducted 24 h later. A, typical images showing the nuclear condensation (arrow) under various treatment conditions as indicated. B and D, LDH release assay; C and E, Hoechst staining. ***, p < 0.001 versus sham treatment; *, p < 0.05; ###, p < 0.001 versus NMDA alone. Note the significantly decreased neuronal death in 12DIV neuron in the presence of SB203580 and the slight increase f in the presence of PD98059, which is more obvious in 3DIV neuron. Bar, 20 μm.