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. Author manuscript; available in PMC: 2021 Nov 20.
Published before final editing as: J Trace Elem Med Biol. 2020 May 20;61:126554. doi: 10.1016/j.jtemb.2020.126554

Figure 1. Summary of the main biological effects of Mn at recommended vs elevated levels:

Figure 1.

Mn2+-alteration of Glu transporters (EAAT), especially GLAST and GLT1 [122], impairs glutamate uptake by astrocytes resulting in an increase in extracellular glutamate concentrations [95]. The net glutamine uptake is also inhibited due to down-regulation of of SNAT1, SNAT2, and SNAT3 expression in astrocytes [90, 96]. The overall effect of manganese on GABAergic synapses is characterized by increased extracellular GABA (GABAEC) levels that is expected to be mediated through inhibition of GAT1 [103]. However, inhibition of astrocytic GAT3 was not supported by the laboratory data [110].

AMPAR - α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; EAAT - Excitatory amino acid transporter; GABA - Gamma-aminobutyric acid; GABA-T - GABA-transaminase; GAD - Glutamate decarboxylase; GAT - GABA transporter; GLAST1 - Glutamate aspartate transporter 1; GLT1 - Glutamate transporter 1; GluR - Glutamate receptor; GOT - Glutamate:oxaloacetate transaminase; NMDAR - N-methyl-D-aspartate receptor; SNAT - Sodium-coupled neutral amino acid transporter; SSADH - Succinic semialdehyde dehydrogenase; VGLUT - Vesicular glutamate transporter