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. 2008 Nov 24;205(12):2781–2789. doi: 10.1084/jem.20081588

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© 2008 Qing et al.

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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Figure 1. — VPA treatment significantly reduces neuritic plaque formation in AD transgenic mice. (A) APP23 mice at the age of 7 or 9 mo and APP23/PS45 double-transgenic mice at the age of 6 wk were treated with 30 mg/kg VPA for 4 wk, whereas age-matched control APP23 mice received the vehicle solution. The mice were killed after behavioral tests and the brains were dissected, fixed, and sectioned. Neuritic plaques were detected using an Aβ-specific monoclonal antibody 4G8 and the DAB method. The plaques were visualized by microscopy with 40X magnification. The number of neuritic plaques was significantly reduced in VPA-treated mice compared with controls. b, d, and f show the representative brain section of the 7-mo APP23 age group, 9-mo APP23 age group, and APP23/PS45 mice treated with VPA, and a, c, and e show their controls, respectively. Black arrows point to plaques. (B) Neuritic plaques were further confirmed using thioflavin S fluorescent staining and visualized by microscopy at 40X magnification. There were less neuritic plaques in VPA-treated mice (b and d) compared with age-matched control mice (a and c). a and b show brain sections of APP23 mice, and c and d show the brain sections of APP23/PS45 mice. White arrows point to green fluorescent neuritic plaques. (C) The brain sections of APP23 were also stained with MAP-2 antibody. VPA treatment significantly increased the number of MAP-2–positive neurites. Bars: (A and B) 400 μm; (C) 200 μm. (D) Quantification of neuritic plaques in APP23 mice with treatment starting at the age of 7 mo, the number represents mean ± SEM. n = 30 mice each. *, P < 0.0001 by Student's t test. (E) Quantification of neuritic plaques in APP23 mice with treatment starting at the age of 9 mo, the number represents mean ± SEM. n = 12 mice each. *, P < 0.005 by Student's t test. (F) Quantification of neuritic plaques in APP23/PS45 mice with treatment starting at the age of 6 wk, the number represents mean ± SEM. n = 25 mice for control and 29 mice for VPA. *, P < 0.0001 by Student's t test.