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. 2011 Oct;179(4):2001–2015. doi: 10.1016/j.ajpath.2011.06.025

Figure 7.

Figure 7

Tau expression causes neuronal loss intimately related to inflammation. A: Timeline of AAV-tauP301L–mediated inflammation. WT mice were intracerebrally injected with AAV-tauP301L and analyzed for GFAP and MHCII at 1½ weeks (n = 4) and 3 weeks (n = 6) after infection. Quantification of GFAP- and MHCII-positive signal in the ipsilateral (white bars) and contralateral (light gray bars) hippocampus and ipsilateral (gray bars) and contralateral (black bars) cortex. Values are given as mean ± SD. B: IHC for MHCII in YFP-expressing mice (n = 6) intracerebrally injected with AAV-tauP301L and analyzed at 21 days after infection. Degenerating neurons are in close proximity to activated microglial cells. Anti-MHCII antibody was followed by rabbit anti-rat biotinylated secondary antibody and Strepta-Alexa 594 (red). YFP-positive neurons are shown in green. C: IHC for GFAP in YFP-expressing mice (n = 6) intracerebrally injected with AAV-tauP301L and analyzed at 21 days after infection. Degenerating neurons are in close proximity to astroglial cells. Anti-GFAP antibody was followed by anti-rabbit biotinylated secondary antibody and Strepta-Alexa 594 (red). YFP-positive neurons are shown in green. Nuclei stained with DAPI are shown in blue. D: In AAV-tauP301L–injected CX3CR1EGFP/EGFP mice (n = 4), the fractalkine receptor–deficient EGFP-positive microglia are recruited to or by the degenerating neurons. Sections were stained for cytoplasmic Nissl substance (red) and nuclei (DAPI, blue). EGFP-positive microglia are shown in green. CA, cornu ammonis; DG, dentate gyrus; SLM, stratum lacunosum moleculare; SO, stratum oriens; SR, stratum radiatum. E: Confocal microscopy of glial markers in AAV-tauP301L–injected CX3CR1EGFP/EGFP mice (n = 4). Microglial markers MHCII and CD11b, unlike astroglial marker GFAP, co-localize with CX3CR1EGFP/EGFP-positive microglia. MHCII, CD11b, CD45, and GFAP were immunodetected using secondary antibody coupled to Alexa 594 (red). EGFP-positive microglia are shown in green, and nuclei stained with DAPI are shown in blue.