Abstract
Abstract
The pathophysiology of many mood disorders is closely related
to abnormal stress response associated with the dysfunction of the
hypothalamic–pituitary–adrenal (HPA) axis and cortisol overproduction. The
hippocampus, a key structure of the limbic system responsible for
both cognitive and emotional spheres, is selectively vulnerable
to excess of glucocorticoids (GCs) inducing neuroinflammation and neurodegeneration.
The antiGC therapy of psychiatric diseases, in particular depressive
disorders, may be a useful additional treatment. Among other approaches,
targeting glucocorticoid receptors, abounded in the hippocampus,
is regarded as highly promising. However, though the preclinical
data provide fairly firm evidence to the concept of antiGC therapy
for stress-related diseases, clinical studies still are at the proof-of-concept
stage. Noteworthy, chronic GC excess is associated not only with
mood diseases, but also with cognitive decline, metabolic disorders,
diabetes. Potentially, antiGC (HPA axis modifying) therapy may alleviate
affective symptoms, cognitive disturbances, GC and insulin resistance
and adverse side effects of conventional drugs through beneficial
effects on the hippocampus mitigating its dysfunction and neurodegeneration,
neuroinflammation, and impairment of neurogenesis. Since stress/GC-associated
neuroinflammation-mediated pathology of the limbic system and, specifically,
the hippocampus, is a general feature typical for many brain diseases,
the concept of antiGC therapy may be extended, tested and validated
in a wider spectrum of cerebral pathologies.