Fig. 2: LpEV treatment improved behavioral deficits of Drd2-KO mice. | Experimental & Molecular Medicine

Fig. 2: LpEV treatment improved behavioral deficits of Drd2-KO mice.

From: Lactobacillus paracasei-derived extracellular vesicles reverse molecular and behavioral deficits in mouse models of autism spectrum disorder

Fig. 2

a, Experimental design. Drd2-KO mice received LpEV (2.27 mg/kg/day or 1.753 × 1012 particles/kg/day, or 50 μg per 22 g body weight per day) orally for 3 weeks and risperidone (0.2 mg/kg/day) was intraperitoneally (i.p.) administered for 7 days, and both treatments continued during behavioral testing as depicted. Behavioral tests were conducted sequentially: social interaction, social preference and repetitive tests. b,c, Locomotion distance (b) and speed (c) of WT, Drd2-KO, Drd2-KO+ LpEV and Drd2-KO + risperidone during the habituation period of the three-chamber social behavior test. All males: WT, 7 animals; Drd2-KO, 6 animals; Drd2-KO + LpEV, 6 animals; Drd2-KO + Risp, 6 animals. Total distance (b), WT versus Drd2-KO versus Drd2-KO + LpEV versus Drd2-KO + Risp. One-way ANOVA, Tukey’s post-hoc test. F(3,21) = 15.49, P < 0.0001. Speed (c), WT versus Drd2-KO versus Drd2-KO + LpEV versus Drd2-KO + Risp. One-way ANOVA, Tukey’s post-hoc test. F(3,21) = 14.64, P < 0.0001. d–g, Social behaviors. Time spent exploring a social target compared to an empty cage (d and f) and time spent exploring a novel stranger versus a familiar one (e and g) in the three-chamber social behavior tests. Data shown for male (d and e) and female (f and g) Drd2-KO mice. Male: WT, 7 animals; Drd2-KO, 6 animals; Drd2-KO + LpEV, 6 animals; and Drd2-KO + risperidone, 6 animals. Female: WT, 7 animals; Drd2-KO, 5 animals; Drd2-KO + LpEV, 6 animals; and Drd2-KO + risperidone, 7 animals. Male (d and e). Sociability (d). WT versus Drd2-KO. Two-way ANOVA, Fisher’s LSD post-hoc test. Genotype, F(1,22) = 0.0504, P = 0.8244; social target, F(1,22) = 16.12, P = 0.0006; genotype × social target, F(1,22) = 4.344, P = 0.0490. Drd2-KO versus Drd2-KO + LpEV. Two-way ANOVA, Fisher’s LSD post-hoc test, LpEV, F(1,20) = 1.678, P = 0.2100; social target, F(1,20) = 12.28, P = 0.0022; LpEV × social target, F(1,20) = 3.500, P = 0.0761. Drd2-KO versus Drd2-KO + risperidone. Two-way ANOVA, Fisher’s LSD post-hoc test, risperidone, F(1,20) = 0.6023, P = 0.4468; social target, F(1,20) = 12.59, P = 0.0020; risperidone × social target, F(1,20) = 3.500, P = 0.0761. Social preference (e). WT versus Drd2-KO. Two-way ANOVA, Fisher’s LSD post-hoc test. Genotype, F(1,22) = 6.194, P = 0.0209; social target, F(1,22) = 10.82, P = 0.0033; genotype × social target, F(1,22) = 8.389, P = 0.0084. Drd2-KO versus Drd2-KO + LpEV. Two-way ANOVA, Fisher’s LSD post-hoc test, LpEV, F(1,20) = 3.568, P = 0.0735; social target, F(1,20) = 3.568, P = 0.0735; LpEV × social target, F(1,20) = 3.762, P = 0.0667. Drd2-KO versus Drd2-KO + risperidone. Two-way ANOVA, Fisher’s LSD post-hoc test, risperidone, F(1,20) = 5.822, P = 0.0256; social target, F(1,20) = 8.186, P = 0.0097; risperidone × social target, F(1,20) = 6.525, P = 0.0189. Female (f and g). Sociability (f). WT versus Drd2-KO. Two-way ANOVA, Fisher’s LSD post-hoc test. Genotype, F(1,20) = 21.04, P = 0.0002; social target, F(1,20) = 89.47, P < 0.0001; genotype × social target, F(1,20) = 31.75, P < 0.0001. Drd2-KO versus Drd2-KO + LpEV. Two-way ANOVA, Fisher’s LSD post-hoc test, LpEV, F(1,18) = 1.242, P = 0.2798; social target, F(1,18) = 14.92, P = 0.0011; LpEV × social target, F(1,18) = 1.562, P = 0.2274. Drd2-KO versus Drd2-KO + risperidone. Two-way ANOVA, Fisher’s LSD post-hoc test, risperidone, F(1,20) = 13.58, P = 0.0015; social target, F(1,20) = 2.720, P = 0.1147; risperidone × social target, F(1,20) = 0.7831, P = 0.3867. Social preference (g). WT versus Drd2-KO. Two-way ANOVA, Fisher’s LSD post-hoc test. Genotype, F(1,20) = 3.117, P = 0.0928; social target, F(1,20) = 1.650, P = 0.2136; genotype × social target, F(1,20) = 5.902, P = 0.0247. Drd2-KO versus Drd2-KO + LpEV. Two-way ANOVA, Fisher’s LSD post-hoc test, LpEV, F(1,18) = 1.396, P = 0.2527; social target, F(1,18) = 3.254, P = 0.0880; LpEV × social target, F(1,18) = 12.57, P = 0.0023. Drd2-KO versus Drd2-KO + risperidone. Two-way ANOVA, Fisher’s LSD post-hoc test, risperidone, F(1,20) = 5.482, P = 0.0297; social target, F(1,20) = 0.02442, P = 0.8774; risperidone × social target, F(1,20) = 1.651, P = 0.2135. h–m, Repetitive behaviors. Time spent by male (h–j) and female (k–m) Drd2-KO mice on self-directed grooming (h and k), rearing (i and l), and digging (j and m). Male: n = 6 animals per group. Female: WT, 7 animals; Drd2-KO, 5 animals; Drd2-KO + LpEV, 5 animals; Drd2-KO + risperidone, 7 animals. Male (h–j): WT versus Drd2-KO versus Drd2-KO + LpEV versus Drd2-KO + risperidone. One-way ANOVA, Tukey’s post-hoc test. Grooming, F(3,20) = 7.421, P = 0.0016; rearing, F(3,20) = 4.392, P = 0.0158; and digging, F(3,20) = 0.3340, P = 0.8009. Female (k–m): WT versus Drd2-KO versus Drd2-KO + LpEV versus Drd2-KO + risperidone. One-way ANOVA, Tukey’s post-hoc test. Grooming, F(3,20) = 7.666, P = 0.0013; rearing, F(3,20) = 5.292, P = 0.0075; and digging, F(3,20) = 1.212, P = 0.3311.

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