Lipopolysaccharide acutely inhibits proliferation of neural precursor cells in the dentate gyrus in adult rats

Lipopolysaccharide (LPS), a bacterial endotoxin released during infection, is known to suppress neurogenesis in the dentate gyrus (DG) in mature rats. The present study aimed to elucidate acute effect of LPS, as well as possible mechanisms involved in the effect, on the neurogenesis in the DG of adult rats. In the first experiment, proliferating cells in the DG were labeled with bromodeoxyuridine (BrdU). Double-labeled immunohistochemistry performed 28 days after the BrdU incorporation revealed co-expression of NeuN, a marker of mature neurons, in most of the BrdU-positive cells in the DG. The rat was injected intraperitoneally with LPS or saline at various intervals after the BrdU incorporation, and BrdU-positive cells were examined 24 h thereafter. The endotoxin reduced the number of BrdU-positive cells that were labeled 24 h before, but not 7 or 28 days before sacrifice, suggesting rapid LPS actions on precursor cells during proliferation, but not after mitosis. In the second experiment, cells in the DG positively stained with BrdU or serine10 phosphorylated histone H3 (pHH3) were examined 5 h after the injection of LPS or saline. BrdU was incorporated 2 h before sacrifice. In these rats, LPS reduced the number of BrdU- or pHH3-positive cells. LPS did not affect the number of terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL)-positive cells within 5, 8 or 24 h. These results indicate that the endotoxin acutely suppresses neurogenesis in the DG in adult rats, presumably by inhibiting proliferation of neural precursor cells, but not by increasing cell death. (C) 2010 Elsevier B.V. All rights reserved.