Details

Autor(en) / Beteiligte

• Hensley, Kenneth
• Abdel-Moaty, Haitham
• Hunter, Jerrod
• Mhatre, Molina
• Mou, Shenyun
• Nguyen, Kim
• Potapova, Tamara
• Pye, Quentin N
• Qi, Min
• Rice, Heather
• Stewart, Charles
• Stroukoff, Katharine
• West, Melinda

Titel

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

Ist Teil von

• Journal of neuroinflammation, 2006-01, Vol.3 (1), p.2-2, Article 2

Ort / Verlag

England: BioMed Central Ltd

Erscheinungsjahr

2006

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 (TNFalpha)-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 TNFalpha 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.