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Low molecular weight chondroitin sulfate ameliorates pathological changes in 5XFAD mice by improving various functions in the brain.
- Source :
-
Neuropharmacology [Neuropharmacology] 2021 Nov 01; Vol. 199, pp. 108796. Date of Electronic Publication: 2021 Sep 20. - Publication Year :
- 2021
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Abstract
- Our previous study found that low molecular weight chondroitin sulfate (LMWCS) had neuroprotective effects against the toxicity of amyloid-β (Aβ) peptides both in vitro and in vivo, and we speculated that the effects might be related with its anti-oxidative activities. In this study, the anti-Alzheimer's disease (AD) activity of LMWCS was further studied in 5XFAD transgenic mice. After 4-month gavage, the levels of Aβ <subscript>1-42</subscript> level, amyloid precursor protein (APP) and presenilin 1 (PS1) were significantly decreased in the brains of 5XFAD mice, indicating the alteration of APP metabolism by LMWCS. Besides, LMWCS inhibited the secretions of pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6. Furthermore, the suppression of neuroinflammation by LMWCS was supported by the decreased expressions of glial fibrillary acidic protein (GFAP) and toll-like receptor 2 (TLR2) in the brains. LMWCS also reduced the production of reactive oxygen species (ROS) and the level of phospho-tau (Ser404) in the brains. Nevertheless, the changes in the behavior tests were moderate. In conclusion, LMWCS administration ameliorated APP metabolism, neuroinflammation, ROS production and tau protein abnormality in the brains of 5XFAD mice, displaying the potential to improve the pathological changes of AD mouse brain. LMWCS could be considered as a promising anti-AD drug candidate, nonetheless, the therapy regimen need to be optimized to improve its pharmacotherapy efficacy.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Alzheimer Disease immunology
Amyloid beta-Peptides drug effects
Amyloid beta-Protein Precursor drug effects
Animals
Behavior, Animal drug effects
Chondroitin Sulfates administration & dosage
Cytokines drug effects
Disease Models, Animal
Mice
Mice, Transgenic
Molecular Weight
Neuroinflammatory Diseases metabolism
Neuroprotective Agents administration & dosage
Oxidative Stress drug effects
Presenilin-1 drug effects
tau Proteins drug effects
Alzheimer Disease drug therapy
Alzheimer Disease metabolism
Chondroitin Sulfates pharmacology
Neuroinflammatory Diseases drug therapy
Neuroinflammatory Diseases immunology
Neuroprotective Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 199
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34543632
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2021.108796