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Fig. 4 | Alzheimer's Research & Therapy

Fig. 4

From: Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer’s disease-associated markers in 3xTg-AD mice

Fig. 4

Cyclophosphamide (CY) modulation of anxiety-like behaviors in 3xTg-AD mice at 2 and 6 months of age. a Performance in the Rotarod remained superior for 3xTg-AD mice (triangles), irrespective of sex, in comparison to age-matched WT controls (circles) (Genotype: F1, 123 = 11.334, p = .001, η2p = .083). Acute or prolonged CY treatment (closed symbols) did not significantly alter the latency to fall off the Rotarod. b Two- and 6-month-old 3xTg-AD males and females swam faster than age-matched WT controls in the Morris water maze acquisition trials (Genotype: F1, 121 = 72.442, p < .001, η2p = .374). CY did not alter the swimming speed of 3xTg-AD mice or WT controls. c From an early age, 3xTg-AD males and females took longer than sex-matched WT controls to descend from an elevated platform in the step-down test, consistent with “acrophobia” (Genotype: F1, 126 = 15.876, p < .001). After several months of CY exposure, 3xTg-AD males, but not WT controls, took longer to complete the step-down test in comparison to vehicle-treated animals, suggesting that prolonged immunosuppression exacerbated anxiety-like behavior (Genotype × Treatment × Sex: F1, 124 = 3.921, p = .05). Sustained CY intake had no discernable impact on the step-down performance of 3xTg-AD females, but WT controls (similar to 3xTg-AD males) took longer to complete the task at 6 months of age. d In the open field test, CY-treated 3xTg-AD males spent the most time immobile in the center of a large open field (Genotype × Treatment × Sex: F1, 123 = 4.092, p = .045). WT Veh males (n = 16), WT CY males (n = 20), 3xTg-AD Veh males (n = 13), 3xTg-AD CY males (n = 17), WT Veh females (n = 18), WT CY females (n = 21), 3xTg-AD Veh females (n = 13), 3xTg-AD CY females (n = 15). Overall group comparisons were carried out using three-way ANOVA (Genotype × Treatment × Sex) followed by post hoc t tests. Error bars = SEM, *p ≤ .05, **p < .01, ***p < .001, # = overall treatment effect, + = Genotype × Treatment × Sex interaction

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