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Title: Studies on the Effect of CMT-3 (COL-3) on Microglia Activation and Expression of Cytokines in the Mouse Brain after Inoculation with a Bacterial Endotoxin, Lipopolysaccharide
Authors: روان عبدالحميد عيدان 
Supervisor: أ.د. يونس لقماني
Keywords: Microglia Cytokines in the Mouse Brain Endotoxin, Lipopolysaccharide
Issue Date: 2012
Publisher:  Kuwait university - college of graduate studies
Abstract: Microglia activation, by tissue damage or exposure to pathogen molecules such as lipopolysaccharide (LPS), results in release of proinflammatory molecules including cytokines, which contribute to neuronal damage in the CNS if not controlled. Tetracyclines such as minocycline inhibit microglial activation and cytokine expression during CNS inflammation. In this study we investigated the potential of a chemically modified tetracycline, COL-3, which is in clinical trials for treatment of malignant tumors, to inhibit LPS-induced glial cell activation and inflammation in the brain. BALB/c female mice (8-12 weeks old, n= 68) were inoculated intraperitoneally with LPS 1 mg/kg or its vehicle. The mice were treated for 3 days with minocycline intraperitoneally. COL- 3 (orally) or their vehicles, commencing 2 days before LPS inoculation. Mice were sacrificed 24 h post LPS inoculation, brains dissected out and the expression of Cd11b (a microglia/macrophage marker), glial fibrillary acidic protein (GFAP, an astrocyte marker), cytokines, iNos and p38 mitogen-activated protein kinase (p38 MAPK) quantified by realtime PCR and/or immunofluorescence. COL-3 treatment significantly inhibited the LPS-induced increase in Cd11b, Tnf-α, Il-12 and Il- 10 transcript levels, showed a tendency to decrease Ifn-γ, Gfap, Il-1β, but did not alter the level of iNos. On the other hand, minocycline treatment significantly reduced LPS-induced increase in Gfap transcripts and showed a tendency to decrease Cd11b, Tnf-α, Il-12, Ifn-γ, Il-1β, Il-10 and iNos. Immunofluorescence imaging showed that both COL-3 and minocycline treatment reduced LPS-induced p38 MAPK, microglia and astrocyte activation. My results show that COL-3 inhibits LPS-induced microglia activation and cytokine up-regulation in the CNS, and displays potential as a therapeutic agent for treatment of conditions involving CNS inflammation.
Appears in Programs:2050 Molecular Biology

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