Glucocorticoid feedback paradox: a homage to Mary Dallman

de Kloet, Edo Ronald

doi:10.1080/10253890.2023.2247090

Cited by 9 publications

(3 citation statements)

References 218 publications

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“…The stress response engulfs different brain regions and levels from molecular to neuronal circuits. "It is the whole brain, not just a small piece of it, that manages stress responses and tries its best to integrate the capacities of the entire mind-body of the organism" [31]. This is absolutely right, and yet we focus on the hippocampus in this review.…”

Section: Discussionmentioning

confidence: 99%

“…CORT 108297, Dazucorilant, or CORT 113176. MIF and related GR antagonists rapidly reverse neurodegeneration and excessive neuronal activation, restore neurogenesis and ameliorate hippocampal cognitive deficits [30,31]. In the rodent hippocampus, MIF and related more selective GR antagonists can rapidly reset markers of proinflammatory activity, excitotoxicity, neuronal activation, and structural features of hippocampal atrophy [31].…”

Section: Mifepristone (Ru 486) As a Prototypic Gr Antagonistmentioning

confidence: 99%

“…MIF and related GR antagonists rapidly reverse neurodegeneration and excessive neuronal activation, restore neurogenesis and ameliorate hippocampal cognitive deficits [30,31]. In the rodent hippocampus, MIF and related more selective GR antagonists can rapidly reset markers of proinflammatory activity, excitotoxicity, neuronal activation, and structural features of hippocampal atrophy [31]. According to a recent analysis [32], MIF is able to "reset" stress system activity as a result of prevention by GR antagonism the damaging effects of high GC concentrations via GR overactivation; continuing rebound suppression of HPA axis activity; action of MIF as an agonist in transrepression promoter of cell-and context-dependent recruitment of coactivators and corepressors in brain stress circuitry; augmentation of brain MR activation and modifying MR:GR balance.…”

Section: Mifepristone (Ru 486) As a Prototypic Gr Antagonistmentioning

confidence: 99%

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Increased Cortisol and Antiglucocorticoid Therapy in Mood Disorders: The Hippocampus as a Potential Drug Target

Gulyaeva

2024

Preprint

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The pathophysiology of many mood disorders is closely related with abnormal stress response associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol overproduction. The hippocampus, 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 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 hippocampal dysfunction and neurodegeneration, neuroinflammation, and 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.

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Section: Discussionmentioning

confidence: 99%