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

Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg(2+)) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. Since there is evidence that Mg(2+) modulates the hypothalamic-pituitary adrenal (HPA) axis, we tes...

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Detalles Bibliográficos
Autores principales: Sartori, S.B., Whittle, N., Hetzenauer, A., Singewald, N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pergamon Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198864/
https://www.ncbi.nlm.nih.gov/pubmed/21835188
http://dx.doi.org/10.1016/j.neuropharm.2011.07.027
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author Sartori, S.B.
Whittle, N.
Hetzenauer, A.
Singewald, N.
author_facet Sartori, S.B.
Whittle, N.
Hetzenauer, A.
Singewald, N.
author_sort Sartori, S.B.
collection PubMed
description Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg(2+)) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. Since there is evidence that Mg(2+) modulates the hypothalamic-pituitary adrenal (HPA) axis, we tested whether enhanced anxiety-like behaviour can be reliably elicited by dietary Mg(2+) deficiency and whether Mg(2+) deficiency is associated with altered HPA axis function. Compared with controls, Mg(2+) deficient mice did indeed display enhanced anxiety-related behaviour in a battery of established anxiety tests. The enhanced anxiety-related behaviour of Mg(2+) deficient mice was sensitive to chronic desipramine treatment in the hyponeophagia test and to acute diazepam treatment in the open arm exposure test. Mg(2+) 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 Mg(2+) deficient mice and its normalisation through diazepam treatment. Overall, the present findings demonstrate the robustness and validity of the Mg(2+) 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’.
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spelling pubmed-31988642012-01-01 Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment Sartori, S.B. Whittle, N. Hetzenauer, A. Singewald, N. Neuropharmacology Article Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg(2+)) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. Since there is evidence that Mg(2+) modulates the hypothalamic-pituitary adrenal (HPA) axis, we tested whether enhanced anxiety-like behaviour can be reliably elicited by dietary Mg(2+) deficiency and whether Mg(2+) deficiency is associated with altered HPA axis function. Compared with controls, Mg(2+) deficient mice did indeed display enhanced anxiety-related behaviour in a battery of established anxiety tests. The enhanced anxiety-related behaviour of Mg(2+) deficient mice was sensitive to chronic desipramine treatment in the hyponeophagia test and to acute diazepam treatment in the open arm exposure test. Mg(2+) 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 Mg(2+) deficient mice and its normalisation through diazepam treatment. Overall, the present findings demonstrate the robustness and validity of the Mg(2+) 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’. Pergamon Press 2012-01 /pmc/articles/PMC3198864/ /pubmed/21835188 http://dx.doi.org/10.1016/j.neuropharm.2011.07.027 Text en © 2012 Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Article
Sartori, S.B.
Whittle, N.
Hetzenauer, A.
Singewald, N.
Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment
title Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment
title_full Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment
title_fullStr Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment
title_full_unstemmed Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment
title_short Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment
title_sort magnesium deficiency induces anxiety and hpa axis dysregulation: modulation by therapeutic drug treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198864/
https://www.ncbi.nlm.nih.gov/pubmed/21835188
http://dx.doi.org/10.1016/j.neuropharm.2011.07.027
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