Concentration Dependent Actions of Glucocorticoids on Neuronal Viability and Survival

Abstract

A growing body of evidence based on experimental data demonstrates that glucocorticoids (GCs) can play a potent role in the survival and death of neurons. However, these observations reflect paradoxical features of GCs, since these adrenal stress hormones are heavily involved in both neurodegenerative and neuroprotective processes. The actual level of GCs appears to have an essential impact in this bimodal action. In the present short review we aim to show the importance of concentration dependent action of GCs on neuronal cell viability and cell survival in the brain. Additionally, we will summarize the possible GC-induced cellular mechanisms at different GC concentrations providing a background for their effect on the fate of nerve cells in conditions that are a challenge to their survival.

Steroids Impact on Myelin Repair, Neurogenesis and Visual Pathway in Multiple Sclerosis: Preclinical Perspectives

“…In contrast, readily available pharmacologic steroids act mainly via transcriptional machinery and cause profound changes in expressions and repressions of steroid responsive genes (Figure 1). Moreover, such steroids homologues or corticosteroids can arrest growth/proliferation of cells, enhance demyelination and neuronal loss, in particular in supra-physiological concentrations [4] (Figure 2). An ensuing injurious effects can permeate to normal white matter and gray matter tissue, and expand the atrophy to subcortical deep gray matter (SDGM) and cerebellar compartments, and may even cause a spinal cord damage, within 3 to 5 years in progressive multiple MS [2,[48][49][50][51], thus probably affecting motor functions as well as innermost workings of the brain.…”

“…On the other hand, steroids can promote infections-partly indirectly through immunosuppression and partly by stimulating steroidresponsive elements in viral/ancillary apoptotic genomes in the nervous system-complicate the disease and potentially mislead the telltale signs of biomarkers in neuro-injury. 1,2,3,6,9,10) and perilous (4,5,7,8) steps during neural injury, and effects of endogenous and exogenous steroids. While pharmacologic steroids can recede infiltrated immune cells and damaging inflammation, can also trigger inhibitory/pro-apoptotic effects leading to profound changes in neuritis and dendrites densities, reparative axonal loss and brain atrophy.…”

“…Steroids are also given in cyclical regimens as a prerequisite to boost the effectiveness of other DMT, such as interferon beta. Corticosteroid effects are highly nonspecific and ubiquitous; can pass blood brain barrier, bind to both glucocorticoid (GR) and mineralocorticoid (MR) receptors in neurons and glial cells in addition to many other cells [4].…”

“…Frequent use of steroids may affect both paraclinical and clinical outcomes. Corticosteroids can be neuroprotective or neurodegenerative in a concentration/dose-response-dependent manner [4].…”

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

“…Physiological levels of GC concentrations offer a balanced environment for neuronal maintenance while both low and high concentrations of GCs may deviate this balance to the neurotoxic range (U-shape-like effect) (Abrahám et al, 2006). The hippocampus appears to be particularly vulnerable to these neurotoxic effects, with CA3 pyramidal neurons being particularly more sensitive compared to CA1 pyramidal cells (Levy et al, 1994).…”