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Fig 1.

Schematic representation of the 4-day drinking in the dark (DID) procedure for 4 weeks.

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Table 1.

Biochemical parameters in the plasma and liver of rats exposed to alcohol during adolescence.

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Fig 2.

Plasma concentrations of chemokines in rats exposed to alcohol during adolescence and control rats grouped by sex.

(A) CCL2 (pg/mL); (B) CX3CL1 (pg/mL); (C) TNF-α (pg/mL); (D) IL-1β (pg/mL); (E) IL-6 (pg/mL); and (F) IL-10 (pg/mL). The bars represent means ± SEM. The bars represent means ± SEM. The data were analyzed by two-way ANOVA and significant main effects or interactions between factors were indicated as follows: (&&&) denotes significant main effect of sex; (##) p<0.01 and (###) p<0.001 denote significant interaction between adolescent alcohol exposure and sex; (aaa) p<0.001 denotes significant differences compared to female control rats after post hoc tests.

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Fig 3.

Representative images after histological analysis of spleen sections using haematoxylin and eosin stain.

Spleen sections are shown at 4x and 40x magnification. Abbreviations: A = Central artery; F = Follicle; MS = Marginal sinus region; MZ = Marginal zone; P = Periarteriolar lymphoid sheath; RP = Red pulp; T = Trabeculus; VS = Venous sinus; WP = White pulp.

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Fig 4.

Relative mRNA expression of endocannabinoid signaling-related proteins in the spleen of rats exposed to alcohol during adolescence and control rats grouped by sex.

(A) CB1 mRNA levels (fold change); (B) CB2 mRNA levels (fold change); (C) PPARα mRNA levels (fold change); (D) NAPE-PLD mRNA levels (fold change); (E) DGLα mRNA levels (fold change); (F) DGLβ mRNA levels (fold change); (G) FAAH mRNA levels (fold change); (H) MGL mRNA levels (fold change); and (I) FAT/CD36 mRNA levels (fold change). The bars represent means ± SEM. The data were analyzed by two-way ANOVA and significant main effects or interaction between factors was indicated as follows: (*) p<0.05 and (**) p<0.01 denote significant main effect of adolescent alcohol exposure; (###) p<0.001 denotes significant interaction between adolescent alcohol exposure and sex. (aaa) p<0.001 denotes significant differences compared to female control rats after post hoc tests; (bbb) p<0.001 denotes significant differences compared to female alcohol-exposed rats after post hoc tests.

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Fig 5.

Expression of CB1, CB2, PPARα and NAPE-PLD proteins in the spleen of rats exposed to alcohol during adolescence and control rats grouped by sex.

Relative protein expression and representative immunoblots of: (A) CB1 protein (fold change); (B) CB2 protein (fold change); (C) PPARα protein (fold change); and (D) NAPE-PLD protein (fold change). Representative immunohistochemical images at 4x magnification of: (E) CB1 protein; (F) CB2 protein; (G) PPARα protein; and (H) NAPE-PLD protein. The bars represent means ± SEM. The data were analyzed by two-way ANOVA and significant main effects or interaction between factors was indicated as follows: (*) p<0.05 denotes significant main effect of adolescent alcohol exposure; (#) p<0.05 denotes significant interaction between adolescent alcohol exposure and sex. (a) p<0.05 and (aa) p<0.01 denote significant differences compared to the respective control rats after post hoc tests; (b) p<0.05 denotes significant differences compared to female alcohol-exposed rats after post hoc tests. The black arrows indicate positive cells. Abbreviations: RP = Red pulp; VS = Venous sinus; WP = White pulp.

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Fig 6.

Representative immunohistochemical images of spleen sections at 10x and 40x magnification of CB1, CB2, PPARα and NAPE-PLD from female control rats.

The squares indicate the areas of 40x magnification. Abbreviations: A = Central artery; F = Follicle; MZ = Marginal zone; P = Periarteriolar lymphoid sheath; RP = Red pulp; VS = Venous sinus; WP = White pulp.

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