Mitigation of Memory Impairment with Fermented Fucoidan and λ-Carrageenan Supplementation through Modulating the Gut Microbiota and Their Metagenome Function in Hippocampal Amyloid-β Infused Rats

Cells. 2022 Jul 26;11(15):2301. doi: 10.3390/cells11152301.

Abstract

Attenuating acetylcholinesterase and insulin/insulin-like growth factor-1 signaling in the hippocampus is associated with Alzheimer's disease (AD) development. Fucoidan and carrageenan are brown and red algae, respectively, with potent antibacterial, anti-inflammatory, antioxidant and antiviral activities. This study examined how low-molecular-weight (MW) and high-MW fucoidan and λ-carrageenan would improve memory impairment in Alzheimer's disease-induced rats caused by an infusion of toxic amyloid-β(Aβ). Fucoidan and λ-carrageenan were dissected into low-MW by Luteolibacter algae and Pseudoalteromonas carrageenovora. Rats receiving an Aβ(25-35) infusion in the CA1 region of the hippocampus were fed dextrin (AD-Con), 1% high-MW fucoidan (AD-F-H), 1% low-MW fucoidan (AD-F-L), 1% high-MW λ-carrageenan (AD-C-H), and 1% low-MW λ-carrageenan (AD-C-L) for six weeks. Rats to receive saline infusion (Normal-Con) had an AD-Con diet. The AD-F-L group showed an improved memory function, which manifested as an enhanced Y-maze spontaneous alternation test, water maze, and passive avoidance tests, similar to the Normal-Con group. AD-F-L also potentiated hippocampal insulin signaling and increased the expression of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the hippocampus. AD-C-L improved the memory function mainly by increasing the BDNF content. AD-F-H and AD-C-H did not improve the memory function. Compared to AD-Con, the ascending order of AD-C-H, AD-F-H, AD-C-L, and AD-F-L increased insulin signaling by enhancing the pSTAT3®pAkt®pGSK-3β pathway. AD-F-L improved glucose tolerance the most. Compared to AD-CON, the AD-F-L treatment increased the serum acetate concentrations and compensated for the defect of cerebral glucose metabolism. AD-Con increased Clostridium, Terrisporobacter and Sporofaciens compared to Normal-Con, and AD-F-L and AD-C-L increased Akkermentia. In conclusion, AD-F-L and AD-C-L alleviated the memory function in the rats with induced AD symptoms by modulating.

Keywords: Alzheimer’s disease; fermentation; fucoidan; short-chain fatty acids; λ-carrageenan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Carrageenan / metabolism
  • Dietary Supplements
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Hippocampus / metabolism
  • Insulin / metabolism
  • Memory Disorders / complications
  • Metagenome
  • Polysaccharides
  • Rats

Substances

  • Amyloid beta-Peptides
  • Brain-Derived Neurotrophic Factor
  • Insulin
  • Polysaccharides
  • Carrageenan
  • fucoidan
  • Acetylcholinesterase

Grants and funding

This study was funded by the National Research Foundation of Korea (2019R1A2C1007203).