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ludc web

Gabriela de Paula

Postdoctoral fellow

ludc web

Methylglyoxal-Mediated Dopamine Depletion, Working Memory Deficit, and Depression-Like Behavior Are Prevented by a Dopamine/Noradrenaline Reuptake Inhibitor

Author

  • Gudrian Ricardo Lopes de Almeida
  • Jozimar Carlos Szczepanik
  • Ingrid Selhorst
  • Ariana Ern Schmitz
  • Bárbara Dos Santos
  • Maurício Peña Cunha
  • Isabella Aparecida Heinrich
  • Gabriela Cristina de Paula
  • Andreza Fabro De Bem
  • Rodrigo Bainy Leal
  • Alcir Luiz Dafre

Summary, in English

Methylglyoxal (MGO) is an endogenous toxin, mainly produced as a by-product of glycolysis that has been associated to aging, Alzheimer's disease, and inflammation. Cell culture studies reported that MGO could impair the glyoxalase, thioredoxin, and glutathione systems. Thus, we investigated the effect of in vivo MGO administration on these systems, but no major changes were observed in the glyoxalase, thioredoxin, and glutathione systems, as evaluated in the prefrontal cortex and the hippocampus of mice. A previous study from our group indicated that MGO administration produced learning/memory deficits and depression-like behavior. Confirming these findings, the tail suspension test indicated that MGO treatment for 7 days leads to depression-like behavior in three different mice strains. MGO treatment for 12 days induced working memory impairment, as evaluated in the Y maze spontaneous alternation test, which was paralleled by low dopamine and serotonin levels in the cerebral cortex. Increased DARPP32 Thr75/Thr34 phosphorylation ratio was observed, suggesting a suppression of phosphatase 1 inhibition, which may be involved in behavioral responses to MGO. Co-treatment with a dopamine/noradrenaline reuptake inhibitor (bupropion, 10 mg/kg, p.o.) reversed the depression-like behavior and working memory impairment and restored the serotonin and dopamine levels in the cerebral cortex. Overall, the cerebral cortex monoaminergic system appears to be a preferential target of MGO toxicity, a new potential therapeutic target that remains to be addressed.

Publishing year

2021

Language

English

Pages

735-749

Publication/Series

Molecular Neurobiology

Volume

58

Document type

Journal article

Publisher

Humana Press

Keywords

  • Animals
  • Bupropion/pharmacology
  • Depression/physiopathology
  • Dopamine/deficiency
  • Dopamine Uptake Inhibitors/pharmacology
  • Female
  • Glutathione/metabolism
  • Immobilization
  • Memory, Short-Term/drug effects
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Motor Activity/drug effects
  • Norepinephrine/metabolism
  • Phosphorylation/drug effects
  • Prefrontal Cortex/drug effects
  • Pyruvaldehyde/administration & dosage
  • Serotonin/metabolism
  • Tyrosine 3-Monooxygenase/metabolism

Status

Published

ISBN/ISSN/Other

  • ISSN: 1559-1182