Back to Search Start Over

Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation

Authors :
Sang Bae Ban
Dong Young Choi
Yong Kyung Lee
Jin Tae Hong
Ki Wan Oh
Dong Yeon Yuk
Jae Woong Lee
Source :
Journal of Neuroinflammation, Vol 5, Iss 1, p 37 (2008), Journal of Neuroinflammation
Publication Year :
2008
Publisher :
BMC, 2008.

Abstract

Background Alzheimer's disease (AD) is characterized by extensive loss of neurons in the brain of AD patients. Intracellular accumulation of beta-amyloid peptide (Aβ) has also shown to occur in AD. Neuro-inflammation has been known to play a role in the pathogenesis of AD. Methods In this study, we investigated neuro-inflammation and amyloidogenesis and memory impairment following the systemic inflammation generated by lipopolysaccharide (LPS) using immunohistochemistry, ELISA, behavioral tests and Western blotting. Results Intraperitoneal injection of LPS, (250 μg/kg) induced memory impairment determined by passive avoidance and water maze tests in mice. Repeated injection of LPS (250 μg/kg, 3 or 7 times) resulted in an accumulation of Aβ1–42 in the hippocampus and cerebralcortex of mice brains through increased β- and γ-secretase activities accompanied with the increased expression of amyloid precursor protein (APP), 99-residue carboxy-terminal fragment of APP (C99) and generation of Aβ1–42 as well as activation of astrocytes in vivo. 3 weeks of pretreatment of sulindac sulfide (3.75 and 7.5 mg/kg, orally), an anti-inflammatory agent, suppressed the LPS-induced amyloidogenesis, memory dysfunction as well as neuronal cell death in vivo. Sulindac sulfide (12.5–50 μM) also suppressed LPS (1 μg/ml)-induced amyloidogenesis in cultured neurons and astrocytes in vitro. Conclusion This study suggests that neuro-inflammatory reaction could contribute to AD pathology, and anti-inflammatory agent could be useful for the prevention of AD.

Details

Language :
English
ISSN :
17422094
Volume :
5
Issue :
1
Database :
OpenAIRE
Journal :
Journal of Neuroinflammation
Accession number :
edsair.doi.dedup.....c1191f47111cf868ff6d053ba6d08ba8