Nguyen-Duong H, Univ. Ulm, 89079 Ulm, Deutschland. Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Disorders of social interactions represent to people living in industrialized societies the most important trigger
for psychological stress. However in assessing their impact, the outstanding feature of the prefrontal cortex
(PFC) is generally not sufficiently taken into account, although it is generally well-established that during
evolution this area was strongly developed, being responsible for the very sophisticated cognitive performance
in humans. Normally PFC held emotions under control by dampening signals sent to subcortical brain regions.
In chronic stressful situations, PFC function might be inhibited resulting in mental blocks and behavioral
disorders. In absence of control signals originating from the PFC, the activity level of the hypothalamuspituitary-
adrenal (HPA) axis is essentially modulated by excitatory and inhibitory inflows from the amygdala
and the hippocampus. Accordingly, following a shift of the control to "subcortical" levels, the amount of
circulating cortisol may depend mainly on the ratio of the antagonistic influences from resp. the amygdala and
the hippocampus. A disturbance of either the positive or the negative feedback loops of the HPA-axis may thus
occur via: 1. a sustained stimulation of the amygdala and/or 2. a decreased expression of hippocampal
glucocorticosteroid receptors (GR). GR expression could possibly be down-regulated on the one hand via an
epigenetic-related shutdown of GR receptor genes and on the other hand via a decrease in intracellular
concentration of Mgi ions; maintaining a physiological intracellular Mgi concentration is essential for
dimerization of the hormone-receptor complex, as a prerequisite for the gene expression. Moreover, since Mgions
are playing a protecting role against overexcitation, this may be beneficial for stabilizing the neuronal
networks responsible for stress-processing. Increasing or normalizing the Mg-levels in the cerebrospinal fluid
might attenuate the activation of glutamate receptors, in such a way that stressors inputs to the amygdala
would exert less influence on the autonomic nervous system and the HPA axis. Orally or parenterally
administered Mg could help correct any dysregulation occurring at glutamatergic synapses localized in the
brain stem according to the ion channel blocking function inherent to Mg ions.