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Fig. 1 | Journal of Biomedical Science

Fig. 1

From: Tetrandrine ameliorates cognitive deficits and mitigates tau aggregation in cell and animal models of tauopathies

Fig. 1

Tetrandrine ameliorates memory dysfunction and tau aggregation in tau mice. A A timeline diagram depicting the drug treatment and experimental plan of the study. Tau mice (Thy1-hTau.P301S, Tg) were treated with saline (Tg-vehicle), and different concentrations of tetrandrine (Tg-TET; 2.5 mg/kg, 5 mg/kg, and 10 mg/kg) via intraperitoneal (i.p.) injections every two days starting when the mice were 2 months old. When the mice reached 4 months old, they were subjected to behavioural and electrophysiological tests and Western blot and immunohistochemical analyses. B The novel object recognition test (NOR) was used to assay memory function. Mice were allowed to freely explore a familiar arena and were exposed to two identical objects (familiar object) prior to the experiment. Representative graphs show the exploration tracks of the mice after one of the objects was replaced by a new object (novel object). The familiar object and novel object are shown as black and green circles, respectively. The wild-type C57 mice spent more time in the exploration zone (shown as a dotted line) of the novel object than the Tg mice. Treatment with tetrandrine increased the exploration of novel objects by Tg mice in a dose-dependent manner. The bar chart depicts the recognition index (RI) calculated by the time the mice spent with each object. Data are summarized as the mean ± SEM from 8 mice in each group. C The contextual fear conditioning test (CFC) was used to assay learning and memory functions. The experiment was conducted as shown on the left. A mouse was placed in a specially designed sound-proof chamber and was stimulated by a foot shock coupled with a cue tone three times. The mice were then assayed in a novel environment with cue tones played after 3 min of exploration or in the same environment without cue tones to assay cue tone-associated and context-associated fear memory. Freezing behaviour represented the recall of memory associated with the electrical shocks. Bar charts depict the percentage of freezing in contextual and cued tests. Data are summarized as the mean ± SEM from 8 mice in each group. D Representative traces showing the electrophysiological fEPSP measurements evoked by 5 trains of theta burst stimulation (TBS) in brain slices isolated from C57 WT mice treated with different concentrations of tetrandrine (Tg-TET) or vehicle (Tg-Vehicle). The bar chart summarizes the fEPSP after TBS stimulation. Data are summarized as the mean ± SEM from 8 mice with 3 brain slices each from each group. E Western blot analyses showing the amount of phosphor-tau protein in Sarkosyl-soluble (SS) and Sarkosyl-insoluble (SI) fractions in wild-type C57 mice (C57 WT) or mice treated with different concentrations of tetrandrine (Tg-TET) or vehicle (Tg-Vehicle) probed with different tau antibodies. Bar charts depict the amount of tau protein normalized to GAPDH in the SS and SI fractions. Data are summarized as the mean ± SEM from 8 mice in each group. *Indicates p < 0.05 compared with the C57 WT group or tau mice treated with saline (Tg-Vehicle)

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