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 TGF?1. The investigation of the role of TGF?1 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 TGF?1 using an adenoviral vector has no significant impact on prion-associated behavioral impairments or on neuropathology. In contrast, inhibition of TGF?1 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 TGF?1 plays a critical role in the downregulation of microglial responses minimizing brain inflammation and thus avoiding exacerbation of brain damage

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.nbd.2006.01.004
ISSNs: 0969-9961 (print)
Related URLs:
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, tgf?1, 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
ePrint ID: 40591
Accepted Date and Publication Date:
June 2006Published
Date Deposited: 07 Jul 2006
Last Modified: 31 Mar 2016 12:11

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