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Fig. 1 | Alzheimer's Research & Therapy

Fig. 1

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

Fig. 1

Cyclophosphamide (CY)-induced alterations in peripheral indicators. a Study design and experimental timeline diagram depicting the age and testing timepoints for data collected. In brief, 1-month-old 3xTg-AD and WT mice of both sexes were randomly assigned to receive treatment with CY or vehicle solution on weekends until 6.5 months of age (n = 13–21 mice/group). All mice were tested in a behavioral battery between 1.5 and 2.5 months of age (2-month timepoint) and re-evaluated between 5.5 and 6.5 months of age (6-month timepoint) to determine the short- and long-term effects of CY treatment. After the behavioral testing was completed, at 6.5 months of age, mice were euthanized and tissues were collected for biomarker assays (see text). b Representative photos showing ruffled and depigmented fur in cyclophosphamide (CY)-treated 3xTg-AD males and a distinct, V-pattern of graying commonly seen in 3xTg-AD females. Alterations in fur quality or condition were not noticeable in CY-exposed WT controls or in vehicle-treated (Veh) groups. c Mice with access to CY on weekends voluntarily ingested similar doses (mg/kg/weekend) of the immunosuppressant at ~ 2 (WT males, 377 ± 37; 3xTg-AD males, 382 ± 20; WT females, 377 ± 36; 3xTg-AD females, 396 ± 30) and ~ 6 months of age (WT males, 323 ± 37; 3xTg-AD males, 390 ± 54; WT females, 300 ± 30; 3xTg-AD females, 364 ± 56). d Sustained exposure to CY (closed symbols), but not vehicle solution (open symbols), induced loss of body mass that was more severe in the 3xTg-AD substrain (triangle) than in WT controls (circles) and became more apparent at older ages (Genotype × Treatment × Week: F1, 120 = 5.55, p < .02). e Prolonged treatment with CY abolished substrain differences in liver weight by ameliorating hepatomegaly evident in Veh-treated 6-month-old 3xTg-AD mice (males: p < .001; females: p < .01). CY also induced more pronounced weight reduction in WT females (p < .001), than in WT males. f Vehicle-treated 3xTg-AD mice of both sexes exhibited spleen enlargement which was prevented in CY-treated conspecifics (males: p < .001; females: p < .001). CY treatment in WT females, but not in WT males, also significantly reduced spleen weights in comparison to the Veh group (p = .005). 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. Body weight comparisons were performed using a repeated measures ANOVA with week as a between-subject factor followed by post hoc ANOVAs at each timepoint. Error bars = SEM, *p ≤ .05, **p < .01, ***p < .001, ‡ = Genotype × Treatment interaction

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