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

Autor: Nigel Whittle, Simone B. Sartori, Alfred Hetzenauer, Nicolas Singewald
Rok vydání: 2012
Předmět:
Male
Corticotropin-Releasing Hormone
Pituitary-Adrenal System
Anxiety
Mice
chemistry.chemical_compound
Corticotropin-releasing hormone
0302 clinical medicine
Corticosterone
Desipramine
Magnesium
Mice
Inbred BALB C
0303 health sciences
Paroxetine
3. Good health
medicine.symptom
Psychology
Proto-Oncogene Proteins c-fos
Corticotropin releasing hormone
medicine.drug
Hypothalamo-Hypophyseal System
medicine.medical_specialty
Fever
Radioimmunoassay
Dark Adaptation
Stress axis
Adrenocorticotropic hormone
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Adrenocorticotropic Hormone
Internal medicine
Selective serotonin re-uptake inhibitor
Reaction Time
medicine
Animals
RNA
Messenger
Protein Precursors
030304 developmental biology
Pharmacology
Analysis of Variance
Diazepam
ACTH
Mice
Inbred C57BL
Disease Models
Animal
Endocrinology
chemistry
Exploratory Behavior
Food Deprivation
Magnesium Deficiency
Stress
Psychological
030217 neurology & neurosurgery
Homeostasis
Zdroj: Neuropharmacology
ISSN: 0028-3908
Popis: 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’.
Highlights ► Robustness and validity of the Mg2+ deficiency model of enhanced anxiety is shown. ► The Mg2+ deficiency model is sensitive to anxiolytic/antidepressant treatments. ► We suggest an inverse relationship between Mg2+ and anxiety. ► An aberrant HPA axis may contribute to the hyper-emotionality of Mg2+ deficiency.
Databáze: OpenAIRE
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