Protection of Cholinergic Neurons against Zinc Toxicity by Glial Cells in Thiamine-Deficient Media

Int J Mol Sci. 2021 Dec 11;22(24):13337. doi: 10.3390/ijms222413337.

Abstract

Brain pathologies evoked by thiamine deficiency can be aggravated by mild zinc excess. Cholinergic neurons are the most susceptible to such cytotoxic signals. Sub-toxic zinc excess aggravates the injury of neuronal SN56 cholinergic cells under mild thiamine deficiency. The excessive cell loss is caused by Zn interference with acetyl-CoA metabolism. The aim of this work was to investigate whether and how astroglial C6 cells alleviated the neurotoxicity of Zn to cultured SN56 cells in thiamine-deficient media. Low Zn concentrations did not affect astroglial C6 and primary glial cell viability in thiamine-deficient conditions. Additionally, parameters of energy metabolism were not significantly changed. Amprolium (a competitive inhibitor of thiamine uptake) augmented thiamine pyrophosphate deficits in cells, while co-treatment with Zn enhanced the toxic effect on acetyl-CoA metabolism. SN56 cholinergic neuronal cells were more susceptible to these combined insults than C6 and primary glial cells, which affected pyruvate dehydrogenase activity and the acetyl-CoA level. A co-culture of SN56 neurons with astroglial cells in thiamine-deficient medium eliminated Zn-evoked neuronal loss. These data indicate that astroglial cells protect neurons against Zn and thiamine deficiency neurotoxicity by preserving the acetyl-CoA level.

Keywords: acetyl-CoA; energy metabolism; thiamine pyrophosphate; zinc toxicity.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cholinergic Neurons / metabolism*
  • Culture Media
  • Mice
  • Neuroglia / metabolism*
  • Thiamine / metabolism
  • Thiamine / pharmacology
  • Thiamine Deficiency / metabolism
  • Thiamine Deficiency / prevention & control*
  • Zinc / toxicity*

Substances

  • Culture Media
  • Zinc
  • Thiamine