Acute hypermethioninemia impairs redox homeostasis and acetylcholinesterase activity in the hippocampus, striatum, and cerebellum of young rats

Int J Dev Neurosci. 2021 May;81(3):285-289. doi: 10.1002/jdn.10098. Epub 2021 Feb 27.

Abstract

Hypermethioninemia is characterized by high plasma concentrations of methionine (Met) and its metabolites, such as methionine sulfoxide (MetO), and neurological changes, such as cerebral edema and cognitive deficits. The aim of this study was to analyze the redox status and acetylcholinesterase (AChE) activity in the hippocampus, striatum, and cerebellum of young Wistar rats subjected to an acute hypermethioninemia protocol. The animals received, by subcutaneous injection, a single dose of Met (0.4 g/kg), MetO (0.1 g/kg), and Met + MetO, and 1 or 3 hr after administration, the animals were euthanatized for brain structure obtaining. In the hippocampus, an increase in lipid peroxidation and glutathione peroxidase (GPx) activity was observed at 1 hr in the MetO and Met + MetO groups, and a reduction in the superoxide dismutase activity was found in the Met + MetO group. Met and/or MetO induced a decrease in the thiol content and GPx activity and enhanced the lipid peroxidation at 3 hr. In the striatum, a reduction in the thiol content and GPx activity, an increase in lipid peroxidation, and AChE activity were induced by Met and/or MetO at 1 or 3 hr. Additionally, in the cerebellum, an increase in the AChE in the MetO and Met + MetO groups 1 hr after administration was observed. These data help to better understand the pathophysiological mechanisms that underlie the neurological changes found in hypermethioninemia patients.

Keywords: cerebellum; hippocampus; methionine; methionine sulfoxide; striatum.

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Amino Acid Metabolism, Inborn Errors / metabolism*
  • Animals
  • Cerebellum / metabolism*
  • Corpus Striatum / metabolism*
  • Glycine N-Methyltransferase / deficiency*
  • Glycine N-Methyltransferase / metabolism
  • Hippocampus / metabolism*
  • Homeostasis / physiology
  • Lipid Peroxidation / physiology
  • Oxidation-Reduction
  • Oxidative Stress / physiology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1 / metabolism

Substances

  • Reactive Oxygen Species
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Glycine N-Methyltransferase
  • Acetylcholinesterase

Supplementary concepts

  • Hypermethioninemia