title: Changes in brain protein expression are linked to magnesium restriction-induced depression-like behavior.
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.
authors.affiliation: Department of Pharmacology and Toxicology and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria.
authors.forename: Nigel
authors.initials: N
authors.lastname: Whittle
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Chen
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Yang
authors.forename: Simone B
authors.initials: SB
authors.lastname: Sartori
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000679:Amygdala / Q000201:enzymology / Q000503:physiopathology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004032:Diet / Q000009:adverse effects; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000201:enzymology / Q000503:physiopathology; D008275:Magnesium Deficiency / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D017374:Paroxetine / Q000008:administration & dosage / Q000627:therapeutic use; D040901:Proteomics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D009569:Nitric Oxide; D017374:Paroxetine; D013482:Superoxide Dismutase; D005969:Glutamate Dehydrogenase; D050995:Voltage-Dependent Anion Channel 1; D000581:Amidohydrolases; C059999:dimethylargininase