Tumor necrosis factor reduces cAMP production in rat microglia

Glia
Mario Patrizio

Abstract

cAMP has been reported to exert a neuroprotective role in several in vivo and in vitro models of brain pathologies, mainly by regulating microglial activation and orienting these cells toward a neuroprotective phenotype. In order to elucidate the intracellular pathways regulated by tumor necrosis factor (TNF) in glial cells, I have studied the modulation of cAMP accumulation by TNF in microglia and astrocyte cultures obtained from the neonatal rat brain. Pre-treatment of microglia with TNF reduced in a dose- and time-dependent manner cAMP accumulation induced by forskolin (FSK), in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX). The TNF inhibitory action was 90% reverted by a neutralizing polyclonal anti-TNF antibody and was not prevented by a 16 h pre-treatment of microglial cultures with the Gi protein inhibitor pertussis toxin (PTx). These results suggest that TNF acts at a step of the cAMP transduction pathway other than receptors, G proteins, and phosphodiesterases. The target of TNF appeared to be adenylyl cyclase, whose ability to synthesize cAMP was markedly reduced (up to 50%) in membranes prepared from TNF-treated microglial cells, both in basal conditions and after stimulation wit...Continue Reading

References

Aug 19, 1991·Neuroscience Letters·H FillitG Wolf-Klein
Dec 1, 1990·Journal of Neuroimmunology·J C GoodmanR K Narayan
Jan 1, 1994·British Journal of Neurosurgery·S A RossB J Rowlands
Jul 1, 1994·Stroke; a Journal of Cerebral Circulation·T LiuG Z Feuerstein
Feb 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·G LeviC Agresti
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Sep 1, 1996·Journal of Neuroimmunology·C X WangJ Gybels
Mar 1, 1996·Brain Research. Molecular Brain Research·L FanT K McIntosh
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·M E GerritsenT Collins
May 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·H UnoM Sugita
Aug 5, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·K HottaC W Emala
Sep 23, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·P Farmer, J Pugin
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·B L BennettD W Anderson
Jul 20, 2002·Progress in Neurobiology·Chen Xu Wang, Ashfaq Shuaib
Jan 1, 2003·Journal of Neuroimmunology·Weihong PanAbba J Kastin
Aug 13, 2003·Journal of Neurochemistry·Ramendra N Saha, Kalipada Pahan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.