Effect of lipopolysaccharide on global gene expression in the immature rat brain.
To improve the understanding of the molecular mechanisms whereby lipopolysaccharide (LPS) affects the immature brain, global gene expression following LPS exposure was investigated in neonatal rats. Brains (n = 5/time point) were sampled 2, 6, and 72 h after LPS and compared with age-matched controls. The mRNA from each brain was analyzed separately on Affymextrix GeneChip Rat Expression Set 230. The number of genes regulated after LPS were 847 at 2 h, 1564 at 6 h, and 1546 genes at 72 h. Gene ontology analysis demonstrated that, at both 2 and 6 h after LPS, genes associated with protein metabolism, response to external stimuli and stress (immune and inflammatory response, chemotaxis) and cell death were overrepresented. At 72 h, the most strongly regulated genes belonged to secretion of neurotransmitters, transport, synaptic transmission, cell migration, and neurogenesis. Several pathways associated with cell death/survival were identified (caspase-tumor necrosis factor alpha [TNF-alpha]-, p53-, and Akt/phosphatidylinositol-3-kinase (PI3 K)-dependent mechanisms). Caspase-3 activity increased and phosphorylation of Akt decreased 8 h after peripheral LPS exposure. These results show a complex cerebral response to peripheral LPS exposure. In addition to the inflammatory response, a significant number of cell death-associated genes were identified, which may contribute to increased vulnerability of the immature brain to hypoxia-ischemia (HI) following LPS exposure.
Eklind
Saskia
S
Department of Obstetrics and Gynecology, Institute for the Health of Women and Children, Göteborg University, Sweden.
Hagberg
Henrik
H
Wang
Xiaoyang
X
Sävman
Karin
K
Leverin
Anna-Lena
AL
Hedtjärn
Maj
M
Mallard
Carina
C
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides