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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Methylene blue inhibits Caspase-6 activity, and reverses Caspase-6-induced cognitive impairment and neuroinflammation in aged mice

Fig. 3

MB treatment improves synaptic function of the hippocampal Schaffer collateral-CA1 pathway in human Casp6 mice. a Experimental design for drug administration, behavioral and electrophysiological study. OFT: open field test, NOR: novel object recognition. b Discrimination NOR index in pre-treated and vehicle-treated KI/Cre (ACL/G n = 4, ACL n = 1), ACL KI/WT (n = 6), WT/Cre (n = 6), or WT/WT (n = 6) mice. Statistical evaluations were done by repeated-measures two-way ANOVA (genotype p < 0.0001, time p = 0.8324, interaction p = 0.4883) and post-hoc Tukey’s analyses pre-treated KI/Cre vs control groups in each treatment *p < 0.05, ** p < 0.01, *** p < 0.001, ****p < 0.0001, vehicle-treated KI/Cre vs control groups # p < 0.05, # # # p < 0.001, and pre-treated vs vehicle-treated (NS). c Discrimination NOR index in pre-treated and MB-treated KI/Cre (ACL/G n = 3, ACL n = 3), ACL KI/WT (n = 3), WT/Cre (n = 5), or WT/WT (n = 5) mice. Statistical evaluations as described in (b). Each symbol represents data from one individual mouse. d&f Top panel: representative traces before and after theta-burst stimulation in vehicle-treated (d) and MB-treated ACL/G KI/Cre (f) and WT/WT. e After/before ratio of the fEPSP slope in vehicle-treated mice (one-way ANOVA p = 0.0003; Dunnett’s post-hoc **p < 0.01 vs WT/WT). d&f Bottom panel: Extracellular fEPSP slope from acute slices of vehicle-treated ACL/G KI/Cre mice (99.967% ± 4.453%, n = 12 slices) and ACL KI/WT, WT/Cre or WT/WT (130.028% ± 3.6611%, n = 46 slices) (d) or MB-treated KI/Cre (141.226% ± 10.955%, n = 9 slices) and KI/WT, WT/Cre or WT/WT mice, control genotypes (132.424% ± 4.78%, n = 43 slices, p = 0.3936). f Arrows indicate time of theta-burst stimulation. The fEPSP recordings from vehicle-treated KI/WT (n = 11 slices), WT/Cre (n = 14 slices) or WT/WT (n = 21 slices) or MB-treated from KI/WT (n = 12 slices), WT/Cre (n = 18 slices) and WT/WT (n = 13 slices) were pooled since they were statistically indistinguishable. g After/before ratio of the fEPSP slope in in MB-treated mice (one-way ANOVA, p = 0.6223)

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