Conference name: 17th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint meeting with the Hungarian Society of Experimental and Clinical Pharmacology (MFT)
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Abstract
Background
Preclinical and some clinical studies suggest a relationship between perturbation
in magnesium 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+ restriction and whether Mg2+ deficiency is associated with altered
HPA axis function.
Methods
Mice assigned to Mg2+-deficient groups were allowed to freely access a 0.005% Mg2+-containing
diet while control mice were fed a normal, 0.2% Mg2+-containing diet. The emotional
behaviour of Mg2+-deficient mice was assessed in a battery of anxiety tests including
the open field test, the light/dark test, the stress-induced hypothermia test, and
the hyponeophagia test. Markers of HPA axis function including CRH gene expression
and plasma ACTH levels were quantified. Neuronal activation patterns in the HPA system
were investigated using mapping of the immediate early gene c-Fos as a marker of neuronal
activation in response to an anxiety-provoking situation.
Results
Compared to controls, Mg2+-deficient mice did indeed display enhanced anxiety-related
behaviour in numerous 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 corticotropin releasing hormone in the paraventricular
hypothalamic nucleus (PVN), which coincided with 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
revealed hyper-excitability in the PVN of anxious Mg2+-deficient mice and its normalisation
through diazepam treatment.
Conclusions
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.
[1
]Department of Pharmacology and Toxicology, Institute of Pharmacy, and Center for Molecular
Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria
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Conference name:
17th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint meeting
with the Hungarian Society of Experimental and Clinical Pharmacology (MFT)