Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment

Abstract

Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg2+) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. Since there is evidence that Mg2+ modulates the hypothalamic-pituitary adrenal (HPA) axis, we tested whether enhanced anxiety-like behaviour can be reliably elicited by dietary Mg2+ deficiency and whether Mg2+ deficiency is associated with altered HPA axis function. Compared with controls, Mg2+ deficient mice did indeed display enhanced anxiety-related behaviour in a battery of established anxiety tests. The enhanced anxiety-related behaviour of Mg2+ deficient mice was sensitive to chronic desipramine treatment in the hyponeophagia test and to acute diazepam treatment in the open arm exposure test. Mg2+ deficiency caused an increase in the transcription of the corticotropin releasing hormone in the paraventricular hypothalamic nucleus (PVN), and elevated ACTH plasma levels, pointing to an enhanced set-point of the HPA axis. Chronic treatment with desipramine reversed the identified abnormalities of the stress axis. Functional mapping of neuronal activity using c-Fos revealed hyper-excitability in the PVN of anxious Mg2+ deficient mice and its normalisation through diazepam treatment. Overall, the present findings demonstrate the robustness and validity of the Mg2+ deficiency model as a mouse model of enhanced anxiety, showing sensitivity to treatment with anxiolytics and antidepressants. It is further suggested that dysregulations in the HPA axis may contribute to the hyper-emotionality in response to dietary induced hypomagnesaemia.This article is part of a Special Issue entitled ‘Anxiety and Depression’.

Algorithm for the diagnosis, treatment, and prevention of stress (for general practitioners)

“…При дефиците Mg 2+ как явном, так и субкомпенсированном проницаемость клеточной мембраны для ионов Na + и Ca 2+ стано-вится патологически усиленной, что приводит: 1) к гипервозбудимости ГГНО, 2) увеличению транскрипции кортикотропин-рилизинг-фактора в паравентрикулярном ядре гипоталамуса, 3) повышению адренокортикотропного гормона плазмы [14,16,17].…”

“…Данные современных зарубежных и российских исследований свидетельствуют о негативном влиянии как дефи-цита магния, так и низкого его содержания в организме [17,33]. Низкое содержание магния в пище приводит к повреждению белков головного мозга и биохимических путей, содействуя диз-регуляции при аффективных расстройствах [34].…”

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

“…Numerous studies have shown that nutritional deficits during fetal and early postnatal development adversely impact upon neural development and behaviour, and dietary Mg deficiency during adulthood exacerbates anxiety-and depressive-like behaviours [19,20] However, there is limited information regarding the potential impact of Mg deficiency during the crucial developmental period, and the potential impact gestational Mg deficiency on adult offspring. In this study, we used a model of moderate maternal Mg deficiency [5] to evaluate the effects of gestational Mg deficiency on hippocampal NMDAR expression and behaviour in offspring.…”

Magnesium Therapy Prevents Senescence with the Reversal of Diabetes and Alzheimer’s Disease

“…Appetite dysregulation and Type 3 diabetes have been linked to higher brain dysregulations (higher cerebral cortex areas) that corrupt the hypothalamus, sympathetic and non-sympathetic nervous system with close connections between magnesium and Sirt1 in the regulation of the circadian rhythm [4] [33], stroke [34]- [37], NAFLD [38]- [40] diabetes [41]- [47] and neurodegenerative diseases [48]- [52].…”