Dietary magnesium restriction reduces amygdala–hypothalamic GluN1 receptor complex levels in mice

Ghafari, Maryam; Whittle, Nigel; Miklósi, András G.; Kotlowski, Caroline; Schmuckermair, Claudia; Berger, Johannes; Bennett, Keiryn L.; Singewald, Nicolas; Lubec, Gert

doi:10.1007/s00429-014-0779-8

Cited by 19 publications

(11 citation statements)

References 51 publications

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“…Similarly, reduced amygdala-hypothalamic protein levels of GluN1-containing NMDA complexes were associated with the depression-like behaviors elicited by dietary magnesium restriction. But chronic paroxetine treatment did not normalize the altered protein levels whereas it improved depression-like behaviors in the magnesium restriction mice [11]. A single dizocilpine dose blocked the reserpine-induced depressive symptoms, but had no effect on the increased levels of GluN1 subunit in the present study, suggesting that this drug targeted the downstream of the NMDA receptor, rather than the receptor per se, as paroxetine did.…”

Section: Discussioncontrasting

confidence: 72%

The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats

Gao

Yang

Huang

et al. 2016

Neuroscience Letters

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Clinical studies have demonstrated that a single dose of ketamine produces complete remission within 24h in some depression patients. The ability of ketamine to produce fast-acting antidepressant-like effects in animal models depends on rapid synthesis of brain-derived neurotrophic factor (BDNF). Here we examined effects of a single dose dizocilpine, a non-competitive NMDA receptor antagonist, on the behavioral and neurobiological changes in rats treated with a single high dose reserpine, which is a monoamine re-uptake blocker and depletes monoamines in the brain with the outcome of depression-like symptoms in animals. A single high dose reserpine (4.0mg/kg) was given to rats intraperitoneally. Forty-eight hours later, the rats showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swim test. Meanwhile, the treatment decreased BDNF levels and neurogenesis in the hippocampus. Pretreatment of a single dose dizocilpine (0.30mg/kg), however, prevented all the reserpine-induced changes, except for GluN1 subunit. These results are suggestive of the involvement of neurogenesis and BDNF in the rapid-acting antidepressant-like behavioral effects of the NMDA receptor antagonists in the reserpinized rats.

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Section: Discussioncontrasting

confidence: 72%

The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats

Gao

Yang

Huang

et al. 2016

Neuroscience Letters

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“…Magnesium gates the activity of NMDA receptors and indeed magnesium restriction is associated with reduced amygdala-hypothalamic protein levels of GluN1-containing NMDA complexes [107,108]. A preclinical study showed that magnesium reduced depressive symptoms and increased the concentration of a NMDA receptor subcomponent (GluN2B) in the prefrontal cortex [109].…”

Section: Special Nutritional Compounds Which Could Influence Depressimentioning

confidence: 99%

Nutritional Aspects of Depression

Lang

Beglinger

Schweinfurth

et al. 2015

Cell Physiol Biochem

213

134

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Several nutrition, food and dietary compounds have been suggested to be involved in the onset and maintenance of depressive disorders and in the severity of depressive symptoms. Nutritional compounds might modulate depression associated biomarkers and parallel the development of depression, obesity and diabetes. In this context, recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin, leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota) acting in gut brain circuits. In this context several healthy foods such as olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy and unprocessed meat have been inversely associated with depression risk and even have been postulated to improve depressive symptoms. In contrast, unhealthy western dietary patterns including the consumption of sweetened beverage, refined food, fried food, processed meat, refined grain, and high fat diary, biscuits, snacking and pastries have been shown to be associated with an increased risk of depression in longitudinal studies. However, it is always difficult to conclude a real prospective causal relationship from these mostly retrospective studies as depressed individuals might also change their eating habits secondarily to their depression. Additionally specific selected nutritional compounds, e.g. calcium, chromium, folate, PUFAs, vitamin D, B12, zinc, magnesium and D-serine have been postulated to be used as ad-on strategies in antidepressant treatment. In this context, dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and treatment strategy for depression. At last, several medications (pioglitazone, metformin, exenatide, atorvastatin, gram-negative antibiotics), which have traditionally been used to treat metabolic disorders showed a certain potential to treat depression in first randomized controlled clinical trials.

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“…Despite this, the reduced maternal Mg availability during gestation had a significant and long-lasting impact upon brain development and behaviour in the adult offspring. Since dietary Mg restriction is associated with alterations in NMDA receptor complexes [29], we next examined the expression of NMDARs during early postnatal life and adulthood, and explored how changes in NMDAR expression may be correlated with altered behaviours.…”

Section: Discussionmentioning

confidence: 99%

Maternal hypomagnesemia alters hippocampal NMDAR subunit expression and programs anxiety-like behaviour in adult offspring

Schlegel

Spiers

Cullen

et al. 2017

Behavioural Brain Research

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.  Maternal Mg deficiency reduced hippocampal GluN1 and GluN2A in male offspring.  Female offspring of Mg-deficient dams had increased GluN1, GluN2A and GluN2B.  Maternal Mg deficiency increased hippocampal GluN2B:GluN2A in adult offspring. AbstractIt is well established that maternal undernutrition and micronutrient deficiencies can lead to altered development and behaviour in offspring. However, few studies have explored the implications of maternal Mg deficiency and programmed behavioural and neurological outcomes in offspring. We used a model of Mg deficiency (prior to and during pregnancy and lactation) in CD1 mice to investigate if maternal Mg deficiency programmed changes in behaviour and NMDAR subunit expression in offspring. Hippocampal tissue was collected at postnatal day 2 (PN2), PN8, PN21 and 6 months, and protein expression of NMDAR subunits GluN1, GluN2A and GluN2B was determined. At 6 months of age, offspring were subject to behavioural tasks testing aspects of anxiety-like behaviour, memory, and neophobia. Maternal hypomagnesemia was associated with increased GluN1, GluN2A and GluN2B subunit expression in female offspring at 6 months, but decreased GluN1 and GluN2A expression in males. The GluN2B:GluN2A expression ratio was increased in both sexes. Male (but not female) offspring from Mg-deficient dams showed anxiety-like behaviour, with reduced head dips (Suok test), and reduced exploration of open arms (elevated plus maze). Both male and female offspring from Mg-deficient dams also showed impaired recognition memory (novel object test). These findings suggest that maternal Mg deficiency can result in behavioural deficits in adult life, and that these changes may be related to alterations in hippocampal NMDA receptor expression.

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Dietary magnesium restriction reduces amygdala–hypothalamic GluN1 receptor complex levels in mice

Cited by 19 publications

References 51 publications

The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats

The influence of dizocilpine on the reserpine-induced behavioral and neurobiological changes in rats

Nutritional Aspects of Depression

Maternal hypomagnesemia alters hippocampal NMDAR subunit expression and programs anxiety-like behaviour in adult offspring

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