Year-end Sale % OFF 
Abstract
BackgroundAlzheimer'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.MethodsIn 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.ResultsIntraperitoneal 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.ConclusionThis study suggests that neuro-inflammatory reaction could contribute to AD pathology, and anti-inflammatory agent could be useful for the prevention of AD.
Highlights
Alzheimer's disease (AD) is characterized by extensive loss of neurons in the brain of AD patients
The anti-inflammatory drug sulindac sulfide inhibited the LPS-induced memory impairment and amyloidogenesis. These results indicate that systemic inflammation induced by LPS could cause memory impairment through enhancement of amyloidogenesis
Our current study showed that systemic inflammatory stimuli elevated amyloidogenesis through activation of β- and γ-secretases accompanied with inhibition of α-secretase leading to elevated Aβ1–42 levels in vivo and in vitro
Summary
Alzheimer's disease (AD) is characterized by extensive loss of neurons in the brain of AD patients. The major neuropathological hallmarks of AD are the formation of senile plaques (SPs) following neurofibrillary tangles (NFTs) which cause neuronal degeneration and synaptic loss. SPs are extracellular deposits of fibrillar and amorphous aggregates of amyloid beta-peptide (Aβ) whereas NFTs are intracellular fibrillar (page number not for citation purposes). AD brains exhibit a number of pathological abnormalities, including a profound loss of synapses, reactive gliosis, and inflammatory processes [2]. Edema and neutrophil invasion, typical features of inflammation, is not seen in the AD brain, tissue levels of inflammatory mediators including cytokines, chemokines, oxygen free radicals and reactive nitrogen species, are altered [5,6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
