Figure 4 : Mefenamic acid is protective in rodent models of Alzheimer’s disease through an anti-inflammatory mechanism.

From: Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models

Figure 4

(a,b) Female Lister hooded rats (200–230 g) received an acute unilateral intracerebroventricular injection of soluble Aβ1–42 on day 0 (5 nmol in 10 μl) which was followed by 14 days (starting one day before surgery) of i.p. injection of mefenamic acid (5 mg kg−1) or vehicle. Animals were then tested in the novel object recognition task on 14 d (a) and 35 d (b) post surgery. Discrimination index data are presented as mean+s.e.m (n=5–10). NS, not significantly different, ###P<0.001 compared with vehicle/vehicle treated animals and **P<0.01 compared to Aβ1-42/vehicle group. (cf) 13–14 month old transgenic mouse model of Alzheimer’s 3 × TgAD and wild-type (WT) control were treated with vehicle or 25 mg kg−1 day−1 mefenamic acid. (c) On day 18 memory was assessed with the novel object recognition task; discrimination index data are presented as mean+s.e.m (n=8–10). ###P<0.001 compared to vehicle/WT animals and **P<0.01 compared with vehicle/3 × TgAD mice. (df) Evaluation of Iba1 and IL-1β expressing microglia within the subicula of 3xTgAD and WT mice following vehicle or mefenamic acid treatment. Microglial activation (d) and IL-1β expression (e) were evaluated and presented as mean+s.e.m (n=8–10). ###P<0.001 compared with vehicle/WT animals and **P<0.01 compared to vehicle/3 × TgAD mice. (f) Representative images of microglial activation and IL-1β co-localization of 3 × TgAD and WT subicula following vehicle or mefenamic acid treatment. Scale bars are 15 μm. Statistical analyses performed using two-way ANOVA followed by Sidak corrected post hoc analysis.