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- Title
NOS2 Gene Deficiency Protects from Sepsis-Induced Long-Term Cognitive Deficits.
- Authors
Weberpals, Marc; Hermes, Michael; Hermann, S.; Kummer, Markus P.; Terwel, Dick; Semmler, Alexander; Berger, Meike; Schäfers, Michael; Heneka, Michael T.
- Abstract
To date, long-term consequences of septic encephalopathy on cerebral metabolism, cognition, learning, and memory capabilities and factors involved are poorly understood. In this study, we used a murine sepsis model to demonstrate that bacterial lipopolysaccharide (LPS) causes long-term cognitive deficits in mice. Two months after LPS treatment, wild-type mice committed more working and reference memory errors than controls. The behavioral impairment was independent of the cerebral glucose uptake as evidenced by 18F-Fluordeoxyglucose small animal positron emission tomography. In contrast, mice deficient for the inducible nitric oxide synthase gene (NOS2-/- ) did not show any cognitive changes when challenged with LPS. Immunohistochemical analysis demonstrated that LPS did not lead to neuronal cell death but caused sustained microglial activation in wild-type as compared to NOS2-/- mice. Expression analysis showed that LPS-treated NOS2-/- mice had lower brain mRNA levels for proinflammatory factors compared with wild-type mice. Expression analysis demonstrated distinct changes in the content of synaptic proteins in wild-type mice, which were not observed in the NOS2-/- mice. Together, this data set outlines the importance of the NOS2 activation for long-term cerebral changes after severe sepsis.
- Subjects
CEREBRAL cortex; COGNITION; ENDOTOXINS; GLUCOSE intolerance; NITRIC oxide; CELL death; MESSENGER RNA
- Publication
Journal of Neuroscience, 2009, Vol 29, Issue 45, p14177
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3238-09.2009