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. Author manuscript; available in PMC: 2018 Jul 10.
Published in final edited form as: Mol Psychiatry. 2017 Jul 11;23(6):1530–1540. doi: 10.1038/mp.2017.142

Figure 1. Synaptic activity stimulation improves, while its inhibition worsens, Tau pathology in vivo.

Figure 1

a Chronic deep brain stimulation (DBS) in 3xTg-AD transgenic mice (Tg-S) resulted in reduced levels of Tau oligomers (middle panels), and increased levels of synaptophysin (upper panels) compared to non-stimulated (Tg-NS) mice, as quantified by confocal immunofluorescence in hippocampal CA1 (scale bars: 10μm; the pattern of synaptophysin immunostaining in WT-S panel appears altered probably because of a tilted angle of cutting and/or perfusion imperfections). b Quantitative analysis showing that levels of synaptophysin are restored to wild-type levels in Tg-S compared to NS-Tg (n=5; one-way ANOVA test, p=0.0045; WT-NS vs Tg-NS **p<0.01; WT-NS vs Tg-S p>0.05). c In Tg-S CA1, levels of Tau-oligomers presented reduced number of puncta (18±3%), puncta area (20±5%) and immunostaining intensity (29±6%) compared to Tg-NS. (two-tailed unpaired t-test, *p<0.05).

d Chronic synaptic inhibition by unilateral deafferentation (Tg-deaff) increased levels of Tau oligomers (middle panels), and reduced levels of synaptophysin (upper panels) compared to undeafferented (Tg-CTRL) somatosensory cortex in PS19 transgenic mice (scale bars: 10μm). e Quantitative analysis showed that levels of synaptophysin are reduced in Tg compared to WT brains, and are further reduced (11±4%) in Tg-deaff compared to Tg-CTRL (n=5; one-way ANOVA test, p<0.0001; WT-CTRL vs Tg-CTRL ****p<0.0001; WT-deaff vs Tg-deaff ****p<0.0001; Tg-CTRL vs Tg-deaff * p<0.05). f Levels of Tau-oligomers showed increased number of puncta (22±8%) and puncta area (18±2%) in Tg-deaff compared to Tg-CTRL (two-tailed paired t-test, *p<0.05, **p<0.01). g DBS decreased levels of phospho-Tau (AT8) in Tg-S compared Tg-NS hippocampi (scale bars: 10μm). Quantitative analysis showed that levels of AT8 are decreased (12±1%) in Tg-S compared to Tg-NS hippocampi of PS19 transgenic mice (n=5; two-tailed unpaired t-test, p=0.028). h Chronic synaptic inhibition increased levels of AT8 in Tg-deaff compared Tg-CTRL somatosensory cortices (scale bars: 10μm). Quantitative analysis showed that levels of AT8 are increased (13±3%) in Tg-deaff compared to Tg-CTRL somatosensory cortex of PS19 transgenic mice (n=5; two-tailed paired t-test, p=0.012). ”n” refers to the number of mice analyzed per each condition. 3xTg mice age: 7 months old; PS19 mice age: 10 months old.