Chitosan oligosaccharides protect rat primary hippocampal neurons from oligomeric β-amyloid 1-42-induced neurotoxicity

Abstract

β-Amyloid peptide (Aβ), the major component of senile plaques in patients with Alzheimer's disease (AD), is believed to facilitate the progressive neurodegeneration that occurs in this disease. Mounting natural compounds are proved to be potential candidates for the prevention and treatment of AD. Chitosan oligosaccharides (COSs), the enzymatic hydrolysates of chitosan, have been reported to possess diverse biological activities. Here we investigated the effect of COSs on oligomeric Aβ-mediated toxicity in rat primary hippocampal neurons. Pretreatment with COSs markedly inhibited cell death induced by Aβ exposure as determined by cell viability assay and lactate dehydrogenase release assay. In parallel, the generation of reactive oxygen species and lipid peroxidation were attenuated by COSs. Furthermore, our results indicated that COSs remarkably prevented Aβ-induced cell apoptosis as manifested by depressing the elevation of Bax/Bcl-2 ratio and caspase-3 activation, suggesting that the neuroprotective effect of COSs could be partially due to apoptosis regulation. In addition, pretreatment with COSs significantly blocked Aβ-induced phosphorylation of c-Jun N-terminal kinase. Taken together, these findings may shed light on the role of COSs as a potential therapeutic agent for AD.

Keywords: 1,1,1,3,3,3-hexafluoro-2-propanol; 2′,7′-dichlorofluorescin diacetate; AD; APP; Alzheimer's disease; Aβ; Aβ42; CCK-8; COSs; Chitosan oligosaccharides; DCFH-DA; HFIP; JNK; LDH; MAPK; MDA; NFTs; Neurotoxicity; ROS; SPs; amyloid precursor protein; c-jun N-terminal kinase; cell counting kit-8; chitosan oligosaccharides; lactate dehydrogenase; malondialdehyde; mitogen activated protein kinase; neurofibrillary tangles; reactive oxygen species; senile plaques; β-Amyloid peptide; β-amyloid fragments 1-42; β-amyloid peptide.