Corticosterone treatment results in enhanced release of peptidergic vesicles in astrocytes via cytoskeletal rearrangements

Abstract

While the effect of stress on neuronal physiology is widely studied, its effect on the functionality of astrocytes is not well understood. We studied the effect of high doses of stress hormone corticosterone, on two physiological properties of astrocytes, i.e., gliotransmission and interastrocytic calcium waves. To study the release of peptidergic vesicles from astrocytes, hippocampal astrocyte cultures were transfected with a plasmid to express pro-atrial natriuretic peptide (ANP) fused with the emerald green fluorescent protein (ANP.emd). The rate of decrease in fluorescence of ANP.emd on application of ionomycin, a calcium ionophore was monitored. Significant increase in the rate of calcium-dependent exocytosis of ANP.emd was observed with the 100 nM and 1 μM corticosterone treatments for 3 h, which depended on the activation of the glucocorticoid receptor. ANP.emd tagged vesicles exhibited increased mobility in astrocyte culture upon corticosterone treatment. Increasing corticosterone concentrations also resulted in concomitant increase in the calcium wave propagation velocity, initiated by focal ATP application. Corticosterone treatment also resulted in increased GFAP expression and F-actin rearrangements. FITC-Phalloidin immunostaining revealed increased formation of cross linked F-actin networks with the 100 nM and 1 μM corticosterone treatment. Alternatively, blockade of actin polymerization and disruption of microtubules prevented the corticosterone-mediated increase in ANP.emd release kinetics. This study reports for the first time the effect of corticosterone on gliotransmission via modulation of cytoskeletal elements. As ANP acts on both neurons and blood vessels, modulation of its release could have functional implications in neurovascular coupling under pathophysiological conditions of stress.

Docosahexaenoic acid (DHA) prevents corticosterone‐induced changes in astrocyte morphology and function

“…Our observations agree well with the very few reports of the effect of corticosterone or stress on the astrocyte cytoskeleton. Chatterjee and Sikdar (2013) showed that incubating cultured rat hippocampus astrocytes for 3 h with 100 nM corticosterone caused the actin cytoskeleton to change and lose stress fibers, as in our model. Such actin remodeling also occurs in other cell types (trabecular meshwork cells, epithelial cells) in response to dexamethasone (Rubenstein et al 2003;Clark et al 2005;Yuan et al 2013).…”

Astrocytes in neuroendocrine systems: An overview

“…In vitro, glucocorticoid treatment induces rapid increases in astrocyte Ca 2+ signalling suggestive of an activation of non‐genomic pathways downstream of glucocorticoid receptors. Glucocorticoid treatment of astrocytes in culture also enhances neuropeptide (ie, atrial natriuretic peptide) release from astrocytes, promotes glutamate recycling, and leads to increases in GFAP‐immunoreactivity and rearrangement of F‐actin fibres, indicative of cellular stress . By contrast, chronic treatment of primary astrocytes in culture with glucocorticoids reduces cellular proliferation and glucocorticoid receptor expression .…”

“…recycling, and leads to increases in GFAP-immunoreactivity and rearrangement of F-actin fibres, indicative of cellular stress. 143,144 By contrast, chronic treatment of primary astrocytes in culture with glucocorticoids reduces cellular proliferation and glucocorticoid receptor expression. 145,146 This is recapitulated in an in vivo rodent model where astrocyte number is reduced in the frontal cortex by chronic HPA axis activation via ACTH administration 145 or in response to chronic corticosterone treatment, with or without additional behavioural stress.…”

The Role of Lactate-Mediated Metabolic Coupling between Astrocytes and Neurons in Long-Term Memory Formation

“…Glucocorticoids appear to synergize with NA in the mobilization of energy during a stress response (Joëls and Baram, 2009 ). Astrocytes express GRs (Bohn et al, 1994 ; Simard et al, 1999 ) and corticotrophin releasing hormone receptors (Kapcala and Dicke, 1992 ), and respond to glucocorticoids with calcium waves (Simard et al, 1999 ) and peptide release (Chatterjee and Sikdar, 2013 ). The breakdown of glycogen following NA stimulation is followed by a seemingly compensatory increase in rates of glycogenesis (Sorg and Magistretti, 1992 ), which is inhibited by dexamethasone (Allaman et al, 2004 ), a synthetic form of glucocorticoid (Sapolsky et al, 2000 ).…”