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Publication : Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein.

First Author  Bellucci A Year  2004
Journal  Am J Pathol Volume  165
Issue  5 Pages  1643-52
PubMed ID  15509534 Mgi Jnum  J:93633
Mgi Id  MGI:3487313 Doi  10.1016/S0002-9440(10)63421-9
Citation  Bellucci A, et al. (2004) Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. Am J Pathol 165(5):1643-52
abstractText  Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant filaments made of hyperphosphorylated tau protein and neurodegeneration leading to nerve cell loss. At 5 months of age, the pathological changes are most marked in brainstem and spinal cord. Here we show that these changes are accompanied by marked neuroinflammation. Many tau-positive nerve cells in brainstem and spinal cord were strongly immunoreactive for interleukin-1beta and cyclooxygenase-2, indicating induction and overproduction of proinflammatory cytokines and enzymes. In parallel, numerous activated microglial cells were present throughout brain and spinal cord of transgenic mice, where they concentrated around tau-positive nerve cells. These findings suggest that inflammation may play a significant role in the events leading to neurodegeneration in the tauopathies and that anti-inflammatory compounds may have therapeutic potential.
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