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Amino Acids

, Volume 40, Issue 4, pp 1231–1248 | Cite as

Changes in brain protein expression are linked to magnesium restriction-induced depression-like behavior

  • Nigel Whittle
  • Lin Li
  • Wei-Qiang Chen
  • Jae-Won Yang
  • Simone B. Sartori
  • Gert LubecEmail author
  • Nicolas Singewald
Original Article

Abstract

There is evidence to suggest that low levels of magnesium (Mg) are associated with affective disorders, however, causality and central neurobiological mechanisms of this link are largely unproven. We have recently shown that mice fed a low Mg-containing diet (10% of daily requirement) display enhanced depression-like behavior sensitive to chronic antidepressant treatment. The aim of the present study was to utilize this model to gain insight into underlying mechanisms by quantifying amygdala/hypothalamus protein expression using gel-based proteomics and correlating changes in protein expression with changes in depression-like behavior. Mice fed Mg-restricted diet displayed reduced brain Mg tissue levels and altered expression of four proteins, N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1), manganese-superoxide dismutase (MnSOD), glutamate dehydrogenase 1 (GDH1) and voltage-dependent anion channel 1. The observed alterations in protein expression may indicate increased nitric oxide production, increased anti-oxidant response to increased oxidative stress and potential alteration in energy metabolism. Aberrant expressions of DDAH1, MnSOD and GDH1 were normalized by chronic paroxetine treatment which also normalized the enhanced depression-like behavior, strengthening the link between the changes in these proteins and depression-like behavior. Collectively, these findings provide first evidence of low magnesium-induced alteration in brain protein levels and biochemical pathways, contributing to central dysregulation in affective disorders.

Keywords

Magnesium restricted diet Amygdala Hypothalamus Depression Gel-based proteomics 

Notes

Acknowledgments

The authors thank Dr. Richard Tessadri for the determination of Mg levels. This work was funded by the FWF (P22931-B18).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

726_2010_758_MOESM1_ESM.pdf (438 kb)
Supplementary material 1 (PDF 438 kb)
726_2010_758_MOESM2_ESM.doc (404 kb)
Supplementary material 2 (DOC 404 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Nigel Whittle
    • 1
    • 2
  • Lin Li
    • 2
  • Wei-Qiang Chen
    • 2
  • Jae-Won Yang
    • 2
  • Simone B. Sartori
    • 1
  • Gert Lubec
    • 2
    Email author
  • Nicolas Singewald
    • 1
  1. 1.Department of Pharmacology and Toxicology and Center for Molecular BiosciencesUniversity of InnsbruckInnsbruckAustria
  2. 2.Department of PediatricsMedical University of ViennaViennaAustria

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