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In inflammatory reactive astrocytes co-cultured with brain endothelial cells nicotine-evoked Ca(2+) transients are attenuated due to interleukin-1beta release and rearrangement of actin filaments.

Journal article
Authors Dick Delbro
Anna Westerlund
Ulrika Björklund
Elisabeth Hansson
Published in Neuroscience
Volume 159
Issue 2
Pages 770-9
ISSN 0306-4522
Publication year 2009
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Pages 770-9
Language en
Keywords Animals, Animals, Newborn, Astrocytes, drug effects, physiology, Brain, cytology, Calcitonin Gene-Related Peptide, pharmacology, Calcium, metabolism, Cells, Cultured, Coculture Techniques, Dose-Response Relationship, Drug, Drug Interactions, Endothelial Cells, drug effects, metabolism, Interleukin-1beta, metabolism, Leptin, pharmacology, Lipopolysaccharides, pharmacology, Male, Microfilaments, physiology, Nicotine, pharmacology, Nicotinic Agonists, pharmacology, Rats, Rats, Sprague-Dawley, Substance P, pharmacology, Time Factors
Subject categories Medical and Health Sciences


The aim of this study was to investigate whether nicotine acetylcholine receptors (nAChRs) are expressed in a more pronounced way in astrocytes co-cultured with microvascular endothelial cells from adult rat brain, compared with monocultured astrocytes, as a sign of a more developed signal transduction system. Also investigated was whether nicotine plays a role in the control of neuroinflammatory reactivity in astrocytes. Ca(2+) imaging experiments were performed using cells loaded with the Ca(2+) indicator Fura-2/AM. Co-cultured astrocytes responded to lower concentrations of nicotine than did monocultured astrocytes, indicating that they are more sensitive to nicotine. Co-cultured astrocytes also expressed a higher selectivity for alpha7nAChR and alpha4/beta2 subunits and evoked higher Ca(2+) transients compared with monocultured astrocytes. The Ca(2+) transients referred to are activators of Ca(2+)-induced Ca(2+) release from intracellular stores, both IP(3) and ryanodine, triggered by influx through receptor channels. The nicotine-induced Ca(2+) transients were attenuated after incubation with the inflammatory mediator lipopolysaccharide (LPS), but were not attenuated after incubation with the pain-transmitting peptides substance P and calcitonin-gene-related peptide, nor with the infection and inflammation stress mediator, leptin. Furthermore, LPS-induced release of interleukin-1beta (IL-1beta) measured by enzyme-linked immunosorbent assay (ELISA) was more pronounced in co-cultured versus monocultured astrocytes. Incubation with both LPS and IL-1beta further attenuated nicotine-induced Ca(2+) response. We also found that LPS and IL-1beta induced rearrangement of the F-actin filaments, as measured with an Alexa488-conjugated phalloidin probe. The rearrangements consisted of increases in ring formations and a more dispersed appearance of the filaments. These results indicate that there is a connection between a dysfunction of nicotine Ca(2+) signaling in inflammatory reactive astrocytes and upregulation of IL-1beta and the rearrangements of actin filaments in the cells.

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