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

Zhengduo Zhang, Hong Wu, Shaojun Qi, Yanjin Tang, Chuan Qin, Rui Liu, Jiacheng Zhang, Yiyao Cao () and Xibao Gao ()
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Zhengduo Zhang: Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Hong Wu: Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Shaojun Qi: Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Yanjin Tang: Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Chuan Qin: Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Rui Liu: Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Jiacheng Zhang: Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Yiyao Cao: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China
Xibao Gao: Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China

IJERPH, 2022, vol. 19, issue 24, 1-15

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 (AlCl 3 ) were investigated. Wistar rats were given an i.p. injection of 60 mg/kg D-gal and 10 mg/kg AlCl 3 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 (Aβ 1-42 ) 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 AlCl 3 -exposed rat model of AD. The inhibition of Aβ 1-42 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; toxicity assessment; human risk; rats; folic acid (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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