Figure 2.

Cellular mechanisms in the neurogenic niche that may be affected by MeHg. Once in the CNS, MeHg reaches the hippocampus and neurogenic niche in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. There are several cellular mechanisms that are believed to be altered and impaired by MeHg in neural stem cells (NSC), causing overall poor neurogenesis. There have been observations that MeHg induces (A) impaired proliferation of NSC, with a decrease of the proliferation markers Ki67 and BrdU, and of the neural stem markers SOX2 and Nestin; (B) impairment of the migration and differentiation of NSC, confirmed by the decrease of the markers DCX, β3-Tubulin, and GFAP; (C) disruption of the maturation of new neurons and apoptosis of the existing ones (neurodegeneration), associated with elevated levels of apoptosis related proteins (Caspase-3 and ERK 1/2) and decrease of proliferation (BrdU) and neuronal markers (MAP-2); (D) increased oxidative stress, evidenced by elevation of reactive oxygen species (ROS) and decrease in NADH and Cytochrome B (Cyt B); and (E) cell cycle arrest, confirmed by the reduction in Ki67 and Cyclin A/D, and cellular senescence of NSC, concomitant with the elevation of the expression of p16 and p21.