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Fig. 4 | Molecular Neurodegeneration

Fig. 4

From: Metformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy

Fig. 4

Metformin reduces tau phosphorylation in mouse cortical neurons via the AMPK-mTOR pathway. Primary cortical neurons were incubated for 6 h with or without 2.5 mM metformin (Met), 10 nM okadaic acid (OA), 10 μM rapamycin (Rapa), and 10 μM dorsomorphin (Dorso) alone or in combination. All treatments were performed in the absence of insulin, except when specifically indicated. a Quantitative analysis of phospho-tau (pTau) in cortical neurons treated with or without metformin in the absence or presence of insulin. b Quantitative analysis of pTau in cortical neurons treated with or without metformin in the absence or presence of okadaic acid. c-d Quantitative analysis of pAMPK (c) and pTau (d) in cortical neurons treated with or without metformin and dorsomorphin alone or in combination. e Quantitative analysis of pS6 in cortical neurons treated with or without metformin in the absence or presence of insulin. f-g. Quantitative analysis of pTau (f) and pS6 (g) in cortical neurons treated with or without metformin and rapamycin. h-i. Quantitative analysis of pS6 (h) and pTau (i) in neurons non-infected (NI), infected with GFP and S16H-Rheb or GFP alone and treated with metformin. Levels of phosphorylated protein were normalized to levels of respective proteins. In panels a, b, d, f, and i, pTau and total tau were analyzed using AT8 and Tau5 antibodies, respectively. In all graphs, bars represent the average ratio ± SEM of 3 independent experiments. *p < 0.05, **p < 0.01, one-way ANOVA followed by Holm-Sidak multiple comparison test

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