Magnesium-deficient diet alters depression- and anxiety-related behavior in mice—influence of desipramine and Hypericum perforatum extract

Singewald, Nicolas; Sinner, Catrin; Hetzenauer, Alfred; Sartori, Simone; Murck, Harald

doi:10.1016/j.neuropharm.2004.08.010

Cited by 136 publications

(114 citation statements)

References 51 publications

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“…For example, dietary zinc restriction rescues the impairment in fear extinction in a mouse model of impaired fear extinction (Whittle et al, 2010). Dietary magnesium restriction induces an increase in anxiety-like behavior in mice (Singewald et al, 2004). Our studies suggest that long-term elevation of brain magnesium might enhance NMDARs functioning selectively in brain regions involved in what was previously described as "top-down control over amygdala" (Rauch et al, 2006) and might help to enhance the efficacy of fear extinction.…”

Section: Regional Specificity Of Mgtsupporting

confidence: 53%

Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

Abumaria¹,

Yin²,

Zhang³

et al. 2011

J. Neurosci.

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Anxiety disorders, such as phobias and posttraumatic stress disorder, are among the most common mental disorders. Cognitive therapy helps in treating these disorders; however, many cases relapse or resist the therapy, which justifies the search for cognitive enhancers that might augment the efficacy of cognitive therapy. Studies suggest that enhancement of plasticity in certain brain regions such as the prefrontal cortex (PFC) and/or hippocampus might enhance the efficacy of cognitive therapy. We found that elevation of brain magnesium, by a novel magnesium compound [magnesium-L-threonate (MgT)], enhances synaptic plasticity in the hippocampus and learning and memory in rats. Here, we show that MgT treatment enhances retention of the extinction of fear memory, without enhancing, impairing, or erasing the original fear memory. We then explored the molecular basis of the effects of MgT treatment on fear memory and extinction. In intact animals, elevation of brain magnesium increased NMDA receptors (NMDARs) signaling, BDNF expression, density of presynaptic puncta, and synaptic plasticity in the PFC but, interestingly, not in the basolateral amygdala. In vitro, elevation of extracellular magnesium concentration increased synaptic NMDAR current and plasticity in the infralimbic PFC, but not in the lateral amygdala, suggesting a difference in their sensitivity to elevation of brain magnesium. The current study suggests that elevation of brain magnesium might be a novel approach for enhancing synaptic plasticity in a regional-specific manner leading to enhancing the efficacy of extinction without enhancing or impairing fear memory formation.

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Section: Regional Specificity Of Mgtsupporting

confidence: 53%

Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

Abumaria¹,

Yin²,

Zhang³

et al. 2011

J. Neurosci.

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“…Taken together, these data indicate that the increased immobility in behavioral despair paradigms is not due to an effect on motor systems, but results from increased depression-related behavior. Increased immobility in the forced swim test has been exhibited by mice and rats in situations that increase vulnerability to depression such as estradiol deficiency due to aromatase knockout (Dalla et al, 2004), stress due to food restriction (Alcaro et al, 2002), magnesium depletion (Singewald et al, 2004), and choline administration (Carlezon et al, 2002). The behavior of the animals in the tail suspension test was not assessed in these studies.…”

Section: Discussionmentioning

confidence: 99%

Chronic Administration of 13-Cis-Retinoic Acid Increases Depression-Related Behavior in Mice

O’Reilly

Shumake

González-Lima

et al. 2006

Neuropsychopharmacol

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Retinoid signaling plays a well-established role in neuronal differentiation, neurite outgrowth, and the patterning of the anteroposterior axis of the developing neural tube. However, there is increasing evidence that nutritional vitamin A status and retinoid signaling play an important role in the function of the adult brain. 13-Cis-retinoic acid (13-cis-RA) (isotretinoin or Accutane), a synthetic retinoid that is an effective oral treatment for severe nodular acne, has been linked with depression and suicide in patients. The purpose of this study was to test the hypothesis that chronic administration of 13-cis-RA would lead to depression-related behaviors in mice. Young, adult male mice received 13-cis-RA (1 mg/kg) by daily intraperitoneal injection for 6 weeks. This treatment paradigm produced plasma levels of 13-cis-RA that are comparable to those reported in human patients taking Accutane. In both the forced swim test and the tail suspension test, we found that 13-cis-RA-treated mice spent significantly more time immobile compared to vehicle-treated controls. In the open field test, there was no change in anxiety-related behavior in 13-cis-RA-treated mice. Furthermore, chronic administration of 13-cis-RA did not impair locomotion in either the open field or the rotarod test. Taken together, these results suggest that administration of 13-cis-RA increases depression-related behaviors in mice.

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“…Mg is another potent antagonist of the NMDA receptor complex (7) and Mg deficiency has been related to symptoms such as agitation, anxiety, irritability and hyperexcitability (8) . In rodent models, Mg depletion increases anxiety and depression-like behaviours (9,10) , and mice with low erythrocyte Mg levels have been found to exhibit more aggressive behaviour than those with high Mg levels (11) .Recently, Jacka et al reported that dietary intakes of Zn and Mg were inversely and cross-sectionally associated with depressive and anxiety scores in a population-based sample of women (n 1046) (12) . Other studies have shown inverse relationships between dietary Zn intakes and depression in women (13)(14)(15)(16) .…”

mentioning

confidence: 99%

Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents

Black

Allen

Jacoby

et al. 2014

Public Health Nutr.

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Objective: Adequate Zn and Mg intakes may be beneficial for the prevention and treatment of mental health problems, such as depression, anxiety and attentiondeficit hyperactivity disorder. We aimed to investigate the prospective association between dietary intakes of Zn and Mg and internalising and externalising behaviour problems in a population-based cohort of adolescents. Design: Prospective analysis (general linear mixed models) of dietary intakes of Zn and Mg assessed using a validated FFQ and mental health symptoms assessed using the Youth Self-Report (YSR), adjusting for sex, physical activity, family income, supplement status, dietary misreporting, BMI, family functioning and energy intake. Setting: Western Australian Pregnancy Cohort (Raine) Study. Subjects: Adolescents (n 684) at the 14-and 17-year follow-ups. Results: Higher dietary intake of Mg (per SD increase) was significantly associated with reduced externalising behaviours (β = −1·45; 95 % CI −2·40, −0·50; P = 0·003). There was a trend towards reduced externalising behaviours with higher Zn intake (per SD increase; β = −0·73; 95 % CI −1·57, 0·10; P = 0·085). Conclusions: The study shows an association between higher dietary Mg intake and reduced externalising behaviour problems in adolescents. We observed a similar trend, although not statistically significant, for Zn intake. Randomised controlled trials are necessary to determine any benefit of micronutrient supplementation in the prevention and treatment of mental health problems in adolescents. Keywords Magnesium Dietary intake Raine Study Mental healthZn and Mg are essential minerals involved in functioning of the central nervous system. Dietary sources of Zn include red meat, poultry, legumes, nuts and seeds, certain types of seafood (e.g. oysters, crab and lobster), whole grains, fortified breakfast cereals and dairy products. Mg is widely distributed in plant foods, particularly green leafy vegetables, legumes, nuts, seeds and whole grains. Zn is a cofactor of many enzymes that play a role in brain function (1) and is present in regions of the brain associated with the pathophysiology of mood disorders, including the amygdala, hippocampus and cerebral cortex (2) . Zn modulates neuronal excitability by inhibiting both the GABA (γ-aminobutyric acid) and NMDA (N-methyl-D-aspartate) receptors (3) and has shown antidepressant-like activities in animal models (4)(5)(6) . Mg is another potent antagonist of the NMDA receptor complex (7) and Mg deficiency has been related to symptoms such as agitation, anxiety, irritability and hyperexcitability (8) . In rodent models, Mg depletion increases anxiety and depression-like behaviours (9,10) , and mice with low erythrocyte Mg levels have been found to exhibit more aggressive behaviour than those with high Mg levels (11) .Recently, Jacka et al. reported that dietary intakes of Zn and Mg were inversely and cross-sectionally associated with depressive and anxiety scores in a population-based sample of women (n 1046) (12) . Other studies have shown...

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Magnesium-deficient diet alters depression- and anxiety-related behavior in mice—influence of desipramine and Hypericum perforatum extract

Cited by 136 publications

References 51 publications

Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

Chronic Administration of 13-Cis-Retinoic Acid Increases Depression-Related Behavior in Mice

Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents

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