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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Pergamon Press
2012
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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’. |
format | Online Article Text |
id | pubmed-3198864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Pergamon Press |
record_format | MEDLINE/PubMed |
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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