TGF-beta1 regulates the inflammatory response during chronic neurodegeneration
Boche, D., Cunningham, C., Docagne, F., Scott, H. and Perry, VH. (2006) TGF-beta1 regulates the inflammatory response during chronic neurodegeneration. Neurobiology Disease, 22, (3), 638-650. (doi:10.1016/j.nbd.2006.01.004).
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The ME7 model of murine prion disease shows an atypical inflammatory response characterized by morphologically activated microglia and an anti-inflammatory cytokine profile with a marked expression of TGFβ1. The investigation of the role of TGFβ1 during a time course disease shows that its expression is correlated with (i) the onset of behavioral abnormalities, (ii) increased activated microglia, (iii) thickening of the basement membrane, and (iv) is associated with increased PrPsc deposition. Increasing TGFβ1 using an adenoviral vector has no significant impact on prion-associated behavioral impairments or on neuropathology. In contrast, inhibition of TGFβ1 activity using an adenovirus expressing decorin induces severe cerebral inflammation, expression of inducible nitric oxide synthase and acute neuronal death in prion-diseased animals only. These data suggest that TGFβ1 plays a critical role in the downregulation of microglial responses minimizing brain inflammation and thus avoiding exacerbation of brain damage
|Keywords:||inflammation, nitric-oxide, transforming growth-factor-beta-1, model, impact, neuropathology, disease, smooth-muscle-cells, neurodegeneration, central-nervous-system, growth-factor-beta, creutzfeldt-jakob-disease, tgf-beta, inos, murine prion disease, chronic neurodegeneration, activation, alzheimers-disease, decorin, tgfβ1, mediated gene-transfer, abnormalities, priori, microglia|
|Subjects:||Q Science > QR Microbiology > QR180 Immunology
R Medicine > RB Pathology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
|Divisions:||University Structure - Pre August 2011 > School of Biological Sciences
University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
|Date Deposited:||07 Jul 2006|
|Last Modified:||02 Mar 2012 12:49|
|Contact Email Address:||D.Boche@soton.ac.uk|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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