Figure 2. Tat-induced synapse loss is both NMDA receptor- and LRP-dependent.
A, Proposed mechanism of Tat-induced synapse loss and death. B, Inhibition of NMDA receptor-mediated increases in [Ca2+]i prevent Tat-induced synapse loss. Bar graph summarizes the effects of inhibitors on changes in PSD95-GFP puncta (PSDs) after 24 h treatment under control (open bars) or Tat-treated (solid bars) conditions. Cultures were treated with 10 µM MK801 or 100 µM BAPTA-AM for 30 min prior to addition of Tat. C, The neurotoxic epitotope of Tat induced synapse loss via an LRP-dependent mechansim. HIV-1 BRU Tat amino acids 32–62 (Tat32–62) induced synapse loss. Tat-induced synapse loss was prevented by the LRP inhibitor, RAP (50 nM) applied 15 min before Tat treatment. Data are expressed as mean ± SEM. *, p<0.01 relative to control; #, p<0.01 relative to Tat alone (Untreated) (ANOVA with Bonferroni post-test).