Neuroprotective effects of magnesium l-threonate in a hypoxic zebrafish model

Young Sung Kim, Young Ju Won, Byung Gun Lim, Too Jae Min, Yeon Hwa Kim, Il Ok Lee

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Background: Hypoxia inhibits the uptake of glutamate (a major neurotransmitter in the brain closely related to cognitive function) into brain cells, and the initial response of cells to cortical hypoxia depends on glutamate. Previous studies have suggested that magnesium may have protective effects against hypoxic injuries. In particular, magnesium l-threonate (MgT) may increase magnesium ion concentrations in the brain better than MgSO4 and improve cognitive function. Methods: We evaluated cell viability under hypoxic conditions in the MgT- and MgSO4-treated human SH-SY5Y neurons, in vivo behavior using the T-maze test following hypoxia in MgT-treated zebrafish, activity of brain mitochondrial dehydrogenase by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and protein expression of the excitatory amino acid transporter (EAAT) 4 glutamate transporter by western blotting. Results: Among the groups treated with hypoxia, cell viability significantly increased when pre-treated with 1 or 10 mM MgT (p = 0.009 and 0.026, respectively). Despite hypoxic insult, MgT-treated zebrafish showed preferences for the red compartment (p = 0.025 for distance and p = 0.007 for frequency of entries), suggesting memory preservation. TTC staining showed reduced cerebral infarction and preserved absorbance in the MgT-treated zebrafish brain after hypoxia (p = 0.010 compared to the hypoxia group). In addition, western blot showed upregulation of EAAT4 protein in the MgT treated group. Conclusions: Pre-treatment with MgT attenuated cell death and cerebral infarction due to hypoxia and protected cognitive function in zebrafish. In addition, MgT appeared to modulate expression of the glutamate transporter, EAAT4.

Original languageEnglish
Article number29
JournalBMC Neuroscience
Issue number1
Publication statusPublished - 2020 Jun 26


  • Behavior
  • Glutamate
  • Hypoxia
  • Magnesium
  • Neuroprotection
  • Zebrafish

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience


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