title: Chitosan oligosaccharides alleviate cognitive deficits in an amyloid-β1-42-induced rat model of Alzheimer's disease.
abstract: OBJECTIVE
  The objective of the present study was two-fold: (i) to evaluate the modulating effects of chitosan oligosaccharides (COS) on cognitive deficits and (ii) to explore their underlying molecular mechanisms.
  
  
  METHODS
  The Morris water maze and passive avoidance tests were used to determine the neuroprotective effects of COS on Aβ1-42-induced learning and memory impairments. Biochemical methods were then used to assess COS antioxidant activity in hippocampus, including effects on apoptosis (TUNEL assay) and changes in inflammatory mediators (immunohistochemistry).
  
  
  RESULTS
  Orally administered COS at 200, 400, or 800 mg/kg doses were effective at reducing the learning and memory deficits in Aβ1-42-induced rats. These same doses were also able to ameliorate neuronal apoptosis. The neuroprotective effects of COS were closely associated with its ability to inhibit oxidative stress. This was shown with decreasing levels of malondialdehyde, 8-hydroxy-2'-deoxyguanosine and increasing levels of glutathione peroxidase and super oxide dismutase activities. COS were also shown to suppress the inflammatory response and decrease measures of inflammation via a decrease in the release of proinflammatory cytokines (e.g. interleukin-1beta and tumor necrosis factor-alpha).
  
  
  CONCLUSIONS
  Taken together, our findings suggest that COS have beneficial effects on the cognitive impairments seen in an Aβ1-42-induced model of Alzheimer's disease via inhibiting oxidative stress and neuroinflammatory responses.
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, PR China.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Jia
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, PR China.
authors.forename: Zhaolan
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: An
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, PR China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, PR China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, PR China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Dai
authors.affiliation: Binzhou Medical University, Yantai 264003, Shandong, China.
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, PR China. Electronic address: sunxx@buu.edu.cn.
authors.forename: Yaxuan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009844:Oligosaccharides / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D009844:Oligosaccharides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D008315:Malondialdehyde; D048271:Chitosan; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Alzheimer's disease; Amyloid-β(1–42); Chitosan oligosaccharides; Neuroinflammation; Oxidative stress