Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein.
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.
Bellucci
Arianna
A
Brain Repair Centre, University of Cambridge, Robinson Way, Cambridge CB2 2PY, UK.
Westwood
Andrew J
AJ
Ingram
Esther
E
Casamenti
Fiorella
F
Goedert
Michel
M
Spillantini
Maria Grazia
MG
D000818:Animals; D001921:Brain / Q000473:pathology; D051546:Cyclooxygenase 2; D005802:Genes, MHC Class II; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D008856:Microscopy, Fluorescence; D009154:Mutation; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors; D019076:Transgenes; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D007375:Interleukin-1; D007527:Isoenzymes; D016875:tau Proteins; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases