Zinc, magnesium and NMDA receptor alterations in the hippocampus of suicide victims

There is evidence for an association between suicidal behavior and depression. Accumulating data suggests that depression is related to a dysfunction of the brain's glutamatergic system, and that the N-methyl-d-aspartate (NMDA) receptor plays an important role in antidepressant activity. Zinc a...

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Bibliographic Details
Published in:Journal of affective disorders Vol. 151; no. 3; pp. 924 - 931
Main Authors: Sowa-Kućma, Magdalena, Szewczyk, Bernadeta, Sadlik, Krystyna, Piekoszewski, Wojciech, Trela, Franciszek, Opoka, Włodzimierz, Poleszak, Ewa, Pilc, Andrzej, Nowak, Gabriel
Format: Journal Article
Language:English
Published: Oxford Elsevier B.V 01.12.2013
Elsevier
Subjects:
Adolescent
Adult
Adult and adolescent clinical studies
Aged
Antidepressant drugs
Antidepressive Agents - metabolism
Biological and medical sciences
Depression
Dizocilpine Maleate - antagonists & inhibitors
Dizocilpine Maleate - metabolism
Female
Hippocampus
Hippocampus - metabolism
Humans
Magnesium
Magnesium - metabolism
Male
Medical sciences
Middle Aged
Miscellaneous
Mood disorders
N-Methylaspartate - metabolism
NMDA receptor
Pathophysiological aspects
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Radioligand Assay
Receptors, N-Methyl-D-Aspartate - metabolism
Suicide
Young Adult
Zinc
Zinc - metabolism
Depression
Magnesium
NMDA receptor
Suicide
Zinc
Hippocampus
Mood disorder
Central nervous system
Glutamate receptor
Inorganic element
Encephalon
Victim
ISSN:0165-0327, 1573-2517, 1573-2517
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Summary:There is evidence for an association between suicidal behavior and depression. Accumulating data suggests that depression is related to a dysfunction of the brain's glutamatergic system, and that the N-methyl-d-aspartate (NMDA) receptor plays an important role in antidepressant activity. Zinc and magnesium, the potent antagonists of the NMDA receptor complex, are involved in the pathophysiology of depression and exhibit antidepressant activity. The present study investigated the potency of Zn2+ and Mg2+ to [3H] MK-801, which binds to the NMDA receptor channel in the hippocampus of suicide victims (n=17) and sudden death controls (n=6). Moreover, the concentrations of zinc and magnesium (by flame atomic absorption spectrometry) and levels of NMDA subunits (NR2A and NR2B) and PSD-95 protein (by Western blotting) were determined. Our results revealed that there was a statistically significant decrease (by 29% and 40%) in the potency of zinc and magnesium (respectively) to inhibit [3H] MK-801 binding to NMDA receptors in the hippocampus in suicide tissue relative to the controls. These alterations were associated with increased NR2A (+68%) and decreases in both the NR2B (−46%) and PSD-95 (−35%) levels. Furthermore, lower concentrations (−9%) of magnesium (although not of zinc) were demonstrated in suicide tissue. Our findings indicate that alterations in the zinc, magnesium and NMDA receptor complex in the hippocampus are potentially involved in the pathophysiology of suicide-related disorders (depression), which may lead to functional NMDA receptor hyperactivity.
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ISSN:0165-0327
1573-2517
1573-2517
DOI:10.1016/j.jad.2013.08.009