Fig. 8.

MEL treatment in rats with chronic GWI enhanced neurogenesis, activated BDNF-ERK-CREB pathway, and reduced synapse loss in the hippocampus. Figures A–F illustrate examples of doublecortin-positive (DCX+) newly born neurons from naïve control (A), GWI-Veh (B), GWI-MEL10 (C), GWI-MEL20 (D), GWI-MEL40 (E), GWI-MEL80 (F) groups. The bar chart G compares the number of DCX+ neurons between different groups. Neurogenesis was decreased in the GWI-Veh group but normalized in the GWI-MEL80 group. GCL, granule cell layer; SGZ, subgranular zone. Scale bar, A-F = 50 μm. The bar charts H-J compare the concentration of BDNF (H) pERK1/2 (I) and p-CREB (J) between different groups. The concentration of all these proteins was decreased in the GWI-Veh group but normalized to the naïve control level in GWI-MEL groups. BDNF was normalized in the GWI-MEL40-80 groups, pERK1/2 was normalized in the GWI-MEL10-20 groups and went above the naïve control level in GWI-MEL40-80 groups. The concentration of p-CREB did normalize to the naïve control level but significantly increased in the GWI-MEL80 group compared to the GWI-Veh group. Figures K–S shows examples of synaptophysin+ (Syn+) and postsynaptic density 95+ (PSD95+) puncta in the dentate molecular layer from naïve control (K–M), GWI-Veh (N–P), GWI-MEL80 (Q–S) groups. The bar charts T-W compare area fraction (AF) of Syn+ and PSD95+ puncta in the dentate molecular layer (T–U) and CA1 subfield (V–W) between different groups. Both Syn+ and PSD95+ puncta were reduced in the GWI-Veh group and normalized to the naïve control level in the GWI-MEL80 group. Scale bar, K–S = 1 μm *, p < 0.05, **, p < 0.01, and ***, p < 0.001; NS, not significant.