Abstract
BackgroundHypoxia 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.MethodsWe 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.ResultsAmong 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.ConclusionsPre-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.
Highlights
Hypoxia inhibits the uptake of glutamate into brain cells, and the initial response of cells to cortical hypoxia depends on glutamate
Previous studies confirmed that the initial response of cells to cortical hypoxia depends on glutamate [8]
We investigated whether magne‐ sium l-threonate (MgT) is associated with neuroprotection and improvement in cognitive function using a hypoxic zebrafish model
Summary
Experimental animal Adult zebrafish (4–6 months old, 2.5–3.5 cm long, 350 ± 50 mg of weight, wild type, Danio rerio) were used in the study. Zebrafish were anesthetized in a water mixture containing 16.8 mg of tricaine per 100 mL, resuspended to minimize the anesthetic time, and administered 1 μL orally of PBS or MgT (10 mM) with a micropipette, taking care not to damage the mouth. This volume was chosen based on pilot data showing that zebrafish were likely to vomit solutions administered at volumes greater than 2 μL. The following day, the absorbance of the DMSO/ethanol solution was measured with a spectrophotometer (Epoch, BioTek instruments, USA) and corrected by the brain weight.
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