Figure 6.

Promoted mobilization and migration of neuronal progenitor cells in EAE mice treated with GA through migratory streams. A, Schematic sagittal representation of the migratory routes from the SVZ through both the RMS (red) and the LCS (yellow). B, Sagittal section through the RMS showing the route of DCX-positive cells (red) from the SVZ to the OB. C, Neuroprogenitors in the LCS, generally functional in the embryonic forebrain and reappear after GA treatment in EAE adult mice. DCX-positive cells (red) migrate alongside the YFP-expressing fibers (green) of the interface between the hippocampus and the corpus callosum toward various cortical regions mainly in the occipital cortex. D, E, Increased mobilization of newly generated neurons visualized with BrdU (orange) and DCX (green) immunostaining in the RMS of EAE+GA mice, compared with EAE mice and naive controls, in an RMS segment adjacent to the SVZ (D) and in a more medial section of the RMS arc (E) (sagittal sections). Scale bar: B, 1000 μm; C, 25; D, 500; E, 50 μm. LV, Lateral ventricle; Ctx, cortex; St, striatum; AC, anterior commissure; cc, corpus callosum; Hip, hippocampus; L-5 and L-6, layers five and six of the cerebral cortex. F–H, Quantitative analysis of BrdU (coexpressing DCX) or DCX in the RMS 1 d (F, G) and 1 month (H) after termination of BrdU and GA injections, indicating a significant increase of neuroprogenitors in the RMS of EAE mice over control, and higher elevation in EAE+GA mice. Note that in one EAE mouse, which exhibited slight, short-term disease and spontaneous recovery (EAE-rec H), enhanced neuronal migration was observed. Quantification was performed by counting the BrdU⁺/DCX⁺ cells and measuring the DCX-stained area (0.2²mm) along the striatal border. The amount of BrdU/DCX-stained cells was averaged from eight sections per mouse, 80 μm apart. Three mice counted per treatment group, except EAE rec, which shows a single mouse. Results are expressed as change fold from naive controls. Control values: BrdU incorporation, 146 ± 31 BrdU⁺/DCX⁺ cells, 1 d after the last BrdU injection; DCX staining, 2193±305 μm², averaged from six naive mice. *p<0.05 versus naive control. EAE mice in B, C, and H were treated with GA subsequent to disease induction, 1 month before perfusion (prevention); in D–G, EAE-induced mice were injected with GA and BrdU 20 d after disease induction, 1–5 d before perfusion (suppression).