2,5-Hexanedione increases the percentage of proliferative Sox2+ cells in rat hippocampus

Abstract

n-Hexane is an organic solvent widely used in industry. 2,5-Hexanedione (2,5-HD), the major neurotoxic metabolite of n-hexane, decreases the levels of neurofilaments (NFs) in neurons. Neurogenesis occurs throughout life, and the hippocampal dentate gyrus is one of two major brain areas showing neurogenesis in adulthood. In the current study, rats were intraperitoneally injected with normal saline solution or 2,5-HD five times per week for five continuous weeks. 2,5-HD was administered to the low-dose and high-dose groups at 200 and 400 mg/kg/day, respectively. Then, immunoreactive cells were counted in the hippocampal granule cell layer (GCL) and subgranular zone (SGZ). Ki67+ cells significantly decreased in the high-dose group, while the percentage of proliferative Sox2+ cells significantly increased, consistent with high hippocampal Sox2 expression. Additionally, western blotting showed that exposure to high doses of 2,5-HD led to decreased NF-L in both the cortex and hippocampus, whereas low doses led to a significant reduction in the cortex only. In conclusion, 2,5-HD increases the percentage of proliferating neural stem and progenitor (Sox2+) cells in the SGZ/GCL.