5-Methyltetrahydrofolate Alleviates Memory Impairment in a Rat Model of Alzheimer's Disease Induced by D-Galactose and Aluminum Chloride

Int J Environ Res Public Health. 2022 Dec 7;19(24):16426. doi: 10.3390/ijerph192416426.

Abstract

The effects of 5-methyltetrahydrofolate (5-MTHF) on a rat model of Alzheimer's disease (AD) induced by D-galactose (D-gal) and aluminum chloride (AlCl3) were investigated. Wistar rats were given an i.p. injection of 60 mg/kg D-gal and 10 mg/kg AlCl3 to induce AD and three doses of 1 mg/kg, 5 mg/kg or 10 mg/kg 5-MTHF by oral gavage. A positive control group was treated with 1 mg/kg donepezil by gavage. Morris water maze performance showed that 5 and 10 mg/kg 5-MTHF significantly decreased escape latency and increased the number of platform crossings and time spent in the target quadrant for AD rats. The administration of 10 mg/kg 5-MTHF decreased the brain content of amyloid β-protein 1-42 (Aβ1-42) and phosphorylated Tau protein (p-Tau) and decreased acetylcholinesterase and nitric oxide synthase activities. Superoxide dismutase activity, vascular endothelial growth factor level and glutamate concentration were increased, and malondialdehyde, endothelin-1, interleukin-6, tumor necrosis factor-alpha and nitric oxide decreased. The administration of 10 mg/kg 5-MTHF also increased the expression of disintegrin and metallopeptidase domain 10 mRNA and decreased the expression of β-site amyloid precursor protein cleavage enzyme 1 mRNA. In summary, 5-MTHF alleviates memory impairment in a D-gal- and AlCl3-exposed rat model of AD. The inhibition of Aβ1-42 and p-Tau release, reduced oxidative stress, the regulation of amyloid precursor protein processing and the release of excitatory amino acids and cytokines may be responsible.

Keywords: ad; folic acid; human risk; rats; toxicity assessment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Aluminum Chloride / toxicity
  • Alzheimer Disease* / chemically induced
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / toxicity
  • Amyloid beta-Protein Precursor / adverse effects
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Disease Models, Animal
  • Galactose / toxicity
  • Hippocampus / metabolism
  • Maze Learning / physiology
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy
  • Oxidative Stress
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • 5-methyltetrahydrofolate
  • Acetylcholinesterase
  • Aluminum Chloride
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Galactose
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A

Grants and funding

This study was supported by the Key Technology Research and Development Program of Shandong Province (grant number: 2019GSF107002), the Zhejiang Province Health Science and Technology Program (grant numbers: 2021KY613, 2022RC120), the Zhejiang Province Public Welfare Technology Application Research Project (grant number: LGC21H260001), and the Zhenan Institute of Radiation Medicine and Nuclear Technology Application Open Project (grant number: ZFY-2021-K-003).