Klotho reduction in CP primes hippocampal microglia for activation.

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Klotho reduction in CP primes hippocampal microglia for activation. Klotho reduction in CP primes hippocampal microglia for activation. (A) Hippocampal sections colabeled for IBA-1 (red) and TMEM119 (green) from 19- to 22-mo-old Klothoflox/flox (Flox) mice obtained 9 mo after i.c.v. injection of AAV5-CMV-Cre (Cre) or AAV5-CMV-GFP (GFP) and imaged by fluorescence microscopy. Mice received i.p. injections of saline (Sal) or ultrapure LPS (1 mg/kg) 28 h and 4 h before sacrifice. [Scale bars: 50 µm (Upper), 25 µm (Lower).] (B–D) Relative hippocampal levels of IBA-1–positive cells (B), IBA-1 fluorescence intensity (C), and TMEM119 to IBA-1 area ratio (D) in mice exposed to these treatments (n = 4 to 8 mice per group). Mean levels in GFP/Sal-treated mice were defined as 1.0. **P < 0.01, ***P < 0.001, and ****P < 0.0001 by two-way ANOVA and Holm-Sidak’s test. Values are means ± SEM. Lei Zhu et al. PNAS 2018;115:48:E11388-E11396 ©2018 by National Academy of Sciences