BMC Neuroscience | |
Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers with synaptic marker loss in rat lipopolysaccharide infusion model of neuroinflammation | |
Jagadeesh S Rao1 Stanley I Rapoport1 Mei Chen1 Vasken L Keleshian1 Mireille Basselin1 Matthew Kellom1 | |
[1] Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg. 9, 1S-126, Bethesda, MD, USA | |
关键词: NF-κB; Neuroinflammation; Phospholipase A2; Synaptophysin; Lipopolysaccharide; Drebrin; Synapse; Cytokine; Arachidonic acid; | |
Others : 1170718 DOI : 10.1186/1471-2202-13-50 |
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received in 2011-12-16, accepted in 2012-05-08, 发布年份 2012 | |
【 摘 要 】
Background
Neuroinflammation, caused by six days of intracerebroventricular infusion of bacterial lipopolysaccharide (LPS), stimulates rat brain arachidonic acid (AA) metabolism. The molecular changes associated with increased AA metabolism are not clear. We examined effects of a six-day infusion of a low-dose (0.5 ng/h) and a high-dose (250 ng/h) of LPS on neuroinflammatory, AA cascade, and pre- and post-synaptic markers in rat brain. We used artificial cerebrospinal fluid-infused brains as controls.
Results
Infusion of low- or high-dose LPS increased brain protein levels of TNFα, and iNOS, without significantly changing GFAP. High-dose LPS infusion upregulated brain protein and mRNA levels of AA cascade markers (cytosolic cPLA2-IVA, secretory sPLA2-V, cyclooxygenase-2 and 5-lipoxygenase), and of transcription factor NF-κB p50 DNA binding activity. Both LPS doses increased cPLA2 and p38 mitogen-activated protein kinase levels, while reducing protein levels of the pre-synaptic marker, synaptophysin. Post-synaptic markers drebrin and PSD95 protein levels were decreased with high- but not low-dose LPS.
Conclusions
Chronic LPS infusion has differential effects, depending on dose, on inflammatory, AA and synaptic markers in rat brain. Neuroinflammation associated with upregulated brain AA metabolism can lead to synaptic dysfunction.
【 授权许可】
2012 Kellom et al.; licensee BioMed Central Ltd.
【 预 览 】
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