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. 2011 Feb 16;31(7):2511–2525. doi: 10.1523/JNEUROSCI.5245-10.2011

Figure 5.

Figure 5.

Spine-synapse density versus expression of pro-aggregant TauRD. A, Bars show quantitative evaluation of spine synapses by electron microscopy in the stratum radiatum of the CA1 hippocampal region of control mice (left), after 10 months expression of pro-aggregant TauRD (middle), and after 10 months switch-on plus 4 months switch-off (right). The synapse density decreases after 10 months of TauRD expression to 74% of control. In the case of 10 months switch-on and 4 months off, the spine synapses are rescued to 90% of control, indicating substantial recovery. bar 1/2, ★★★p = 0.000031; bar 2/3, ★p = 0.018; bar 1/3, p = 0.062. B, Western blots showing expression of Tau variants and synaptic proteins in wild-type mice (14 months old), pro-aggregant ON mice (14 months TauRD/ΔK280 expression), and pro-aggregant OFF mice (10 months ON plus 4 months OFF TauRD/ΔK280 expression). Decreased levels of PSD95, drebrin, synaptophysin, and NMDAR1 in pro-aggregant ON mice compared to wild-type mice are shown. Note that the levels of synaptic proteins are partly rescued after the switch off for 4 months. C, Densitometric analysis of the Western blots (B) for the synaptic proteins (synaptophysin, drebrin, PSD95, and NMDAR1), all normalized to β-actin (n = 4). The gray bars indicate the reduction of the synaptic proteins after TauRD/ΔK280 expression in the pro-aggregant ON mice to ∼40% compared with control mice. The black bars show the rescue of synaptic proteins in 4 months switched off pro-aggregant OFF mice to ∼70%, compared with control mice. Significance tests (two-sided t tests) resulted in p values of 0.0176 (synaptophysin), 0.0828 (drebrin), 0.0217 (PSD95), and 0.0133 (NMDAR1) for the differences between wild-type and Pro_ON, resulting in an overall p value of 0.000273 (highly significant) according to Fisher's combined probability test. Similarly, the combined p value for Pro_ON versus Pro_OFF was 0.0319 (significant), whereas the difference between wild-type and Pro-OFF was not significant (combined p value 0.203). Pro-aggr., pro-aggregant; S'physin, synaptophysin. The data in A and C are means ± SEM.