Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammationReportar como inadecuado




Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Neuroinflammation

, 3:2

First Online: 25 January 2006Received: 01 September 2005Accepted: 25 January 2006

Abstract

Detailed study of glial inflammation has been hindered by lack of cell culture systems that spontaneously demonstrate the -neuroinflammatory phenotype-. Mice expressing a glycine → alanine substitution in cytosolic Cu, Zn-superoxide dismutase G93A-SOD1 associated with familial amyotrophic lateral sclerosis ALS demonstrate age-dependent neuroinflammation associated with broad-spectrum cytokine, eicosanoid and oxidant production. In order to more precisely study the cellular mechanisms underlying glial activation in the G93A-SOD1 mouse, primary astrocytes were cultured from 7 day mouse neonates. At this age, G93A-SOD1 mice demonstrated no in vivo hallmarks of neuroinflammation. Nonetheless astrocytes cultured from G93A-SOD1 but not wild-type human SOD1-expressing transgenic mouse pups demonstrated a significant elevation in either the basal or the tumor necrosis alpha TNFα-stimulated levels of proinflammatory eicosanoids prostaglandin E2 PGE2 and leukotriene B4 LTB4; inducible nitric oxide synthase iNOS and •NO indexed by nitrite release into the culture medium; and protein carbonyl products. Specific cytokine- and TNFα death-receptor-associated components were similarly upregulated in cultured G93A-SOD1 cells as assessed by multiprobe ribonuclease protection assays RPAs for their mRNA transcripts. Thus, endogenous glial expression of G93A-SOD1 produces a metastable condition in which glia are more prone to enter an activated neuroinflammatory state associated with broad-spectrum increased production of paracrine-acting substances. These findings support a role for active glial involvement in ALS and may provide a useful cell culture tool for the study of glial inflammation.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-2094-3-2 contains supplementary material, which is available to authorized users.

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Autor: Kenneth Hensley - Haitham Abdel-Moaty - Jerrod Hunter - Molina Mhatre - Shenyun Mou - Kim Nguyen - Tamara Potapova - Quenti

Fuente: https://link.springer.com/







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