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

Abstract

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.

Anxiolytic effects of Formononetin in an inflammatory pain mouse model

“…The following experiments were focused on the BLA of amygdala, because, according to behavioral studies, the BLA is implicated in the onset and development of anxiety [30], a behavioral abnormality that has been associated with synaptic changes [31] and expression alteration of NMDAR [32]. The levels of NMDAR in the BLA of mice were examined on the 16th day (Fig.…”

Placental adaptations to micronutrient dysregulation in the programming of chronic disease

“…Magnesium deficiency has been shown to impair foetal growth and alter kidney function leading to increased urination in the offspring . Furthermore, magnesium deficiency during pregnancy in mice has been shown to induce anxiety like behaviour in adulthood . A population based birth cohort study demonstrated that maternal zinc deficiency is associated with foetal growth restriction .…”

“…15 Furthermore, magnesium deficiency during pregnancy in mice has been shown to induce anxiety like behaviour in adulthood. 16 A population based birth cohort study demonstrated that maternal zinc deficiency is associated with foetal growth restriction. 17 Furthermore, zinc deficiency in rats during the pre and postnatal period induced sex specific vascular dysfunction in offspring.…”

“…76 Magnesium (Mg) 350 mg Increased risk of preterm birth, ↓ birth weight and preeclampsia 31 in humans. Animal models demonstrate foetal loss, placental abnormalities 89 as well as anxiety and renal dysfunction in offspring 15,16 Rare inducement of toxicity, positive effects on bone mineral density, neuroprotection. 31 Magnesium sulphate is the standard treatment to reduce incidence of eclampsia in women with preeclampsia and reduces risk of cerebral palsy 90 Active materno-foetal transport at average rate of 4.5 mg/day maintaining high foetal plasma levels, mother will retain Mg at foetal expense when deficient.…”

Magnesium supplementation during pregnancy

“…Магнийдефицитное состояние в период беременно-сти значимо приводит к повышению до-и постимпланта-ционной гибели плодов, снижает их массу и размеры [26]. Кроме того, доказано, что гипомагнезиемия у матери во время беременности приводит к нарушениям памяти у потомства [27]. В то же время прием препаратов магния во время беременности значительно снижает риск раз-вития синдрома задержки роста плода, а также уровень провоспалительных цитокинов в амниотической жидко-сти и плаценте [28].…”