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. Author manuscript; available in PMC: 2014 Sep 27.
Published in final edited form as: Cell Rep. 2014 May 10;7(4):1065–1076. doi: 10.1016/j.celrep.2014.03.076

Figure 7. Treatment with GluN2B selective antagonists blocks klotho effects on NMDAR currents and cognition.

Figure 7

(A,B) Representative traces (A) and quantitation (B) of isolated NMDAR EPSCs in the presence of NBQX (10 μm) at baseline (black) and following perfusion with ifenprodil (Ifen., 3 μM) (red) in the same slices. Number of slices/mice: NTG 6/3, KL 5/3. Two-way repeated measures ANOVA: ifenprodil effect p<0.0001, ifenprodil by KL interaction p<0.05. (C) Time course of NMDAR EPSC decay constant following ifenprodil perfusion in each genotype. Mixed model ANOVA: p<0.0001 for KL vs NTG genotype by time effect. (D) Change in decay constant (τ) between 0-10 min after initiation of ifenprodil treatment in NTG and KL slices. Number of slices/number of mice: NTG 7/3, KL 5/3. (E-F) Mice (n=8-19 per group) received a single i.p. injection of vehicle (−) or ifenprodil (5 mg/kg) 10 min before training in a fear conditioning paradigm or testing in the Y-maze. (E) Percent time mice (age 5-7 months) spent freezing at baseline and 24 h after context training in a fear conditioning task. Two-way ANOVA: ifenprodil by KL interaction p<0.05. (F) Percent alternations among Y-maze arms that mice (age 10-12 months) showed during 3 min exploration. Two-way ANOVA: ifenprodil by KL interaction p<0.09. (G-H) Mice (n=13-19 per group, age 3-5 months) received a single i.p. injection of vehicle (−) or Ro 25-6981 (Ro 25; 5 mg/kg) 30 min before testing in Y-maze. (G) Percent alternations among Y-maze arms. Two-way ANOVA: Ro 25 by KL interaction p<0.05. (H) Percent decrease in alternations following Ro 25 treatment in NTG and KL mice. *p<0.05, **p<0.01, ***p<0.001 vs. NTG or as indicated by brackets by t-test (B, D, H) or Bonferroni-Holm test (E, F, G). See also Figure S6. Data are means ± SEM.