Exploring the effects of embryonic and neonatal exposure to lipopolysaccharides on oligodendrocyte differentiation in the rat hippocampus and the protective effect of alpha-glycosyl isoquercitrin.

J Chem Neuroanat

Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan; Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan; Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. Electronic address:

Published: November 2023

This study compared the effects of embryonic and neonatal lipopolysaccharides (LPS) exposure (E-LPS and N-LPS) on oligodendrocyte (OL) differentiation in the hippocampus of male rats and explored the protective effect of the antioxidant alpha-glycosyl isoquercitrin (AGIQ). Using SD rats, LPS exposure occurred either intraperitoneally in dams between gestational days 15 and 16 (50 µg/kg body weight/time) or in male pups on postnatal day (PND) 3 (1 mg/kg body weight). Under both regimens, AGIQ at 0.5% (w/w) was supplemented, to dams from the gestation period (before LPS exposure) until weaning on PND 21 and to male offspring from weaning until PND 77 (adulthood). Compared with a control treatment, E-LPS treatment resulted in fewer NG2 OL progenitor cells (OPCs) and an upregulation of Tcf4 at PND 6; by PND 21, low NG2 OPC number persisted, but OLIG2 OL lineage cells increased, while CNPase mature OLs counts were unchanged. By contrast, N-LPS treatment resulted in fewer OLIG2 cells and an upregulation of Bmp4 at PND 6; by PND 21, NG2 OPCs decreased, while GFAP astrocytes increased at both PND 6 and 21. After N-LPS treatment, Kl and Yy1 were downregulated and there were fewer Klotho and CNPase cells at PND 21. Results suggest that E-LPS treatment facilitates OPC differentiation into pre- and immature OLs until weaning, while N-LPS treatment suppresses OPC differentiation into mature OLs but facilitates astrocyte generation; however, these changes spontaneously recovered by adulthood under both regimens. AGIQ treatment ameliorated the effects of LPS treatment of both regimens, suggesting that LPS-induced disruption of OPC/OL differentiation occurs via neuroinflammation.

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http://dx.doi.org/10.1016/j.jchemneu.2023.102336DOI Listing

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