Fig. 1.

PAE and OMD mice exhibit significant deficits in motor-skill learning. (A) STZ or CB was injected into P42 mice 14 d before gestational onset to obtain MD and MD-control mice, respectively. Arrows indicate timepoints of metabolic and physical assessments. (B) Note that 25% ethanol (in PBS) or PBS was injected into gestating P56 mice at E16.5 and 17.5 to obtain alcohol-exposed (AE) and AE-control mothers. (C–H) No significant difference in body weight between MD and MD-controls [C, Treatment: F(1, 5) = 0.3166, P = 0.5980, Days: F(4, 20) = 0.5091, P = 0.7297, Interaction: F(4, 20) = 2.817, P = 0.0527]. Compared to MD-controls, random blood glucose levels were significantly elevated in MD mice at 12 and 14 d post STZ injection in fasting [D, Treatment × Days interaction: F(4, 20) = 3.784, P = 0.0190], but not in the non-fasting condition [E, Treatment: F(1, 5) = 4.146, P = 0.0973, Day: F(4, 20) = 3.128, P = 0.0376, Interaction: F(4, 20) = 1.923, P = 0.1459]. Body weight increased similarly in MD and MD-controls during pregnancy [F, Treatment: F(1, 5) = 0.05422, P = 0.8251, Days: F(4, 20) = 75.95, P < 0.0001, Interaction: F(4, 20) = 0.5466, P = 0.7036]. Compared to MD-control, random blood glucose levels in pregnant MD mice were significantly elevated during E5.5–17.5 in the non-fasting condition [H, Treatment × Days interaction: F(4, 20) = 3.551, P = 0.0241]. Random blood glucose levels in pregnant MD mice were higher, but not significantly so, in the fasting condition [G, Treatment: F(1, 5) = 4.85, P = 0.0789; Days: F(4, 20) = 0.8769, P = 0.4952; and Treatment × Days interaction: F(4, 20) = 0.6711, P = 0.6197]. (I) Accelerated rotarod test schematic. (J) Initial motor coordination (terminal speed at trial 1) was unaffected in PAE and OMD (PAE vs. PAE-control, P = 0.1838; OMD vs. OMD-control, P = 0.2960; Kruskal–Wallis test). Changes in terminal speed of PAE and OMD mice between first and last (sixth) trials were significantly smaller than those of controls (PAE vs. PAE-control, P = 0.0044; OMD vs. OMD-control, P = 0.0035; two-tailed Student’s t-test). (K) Learning-index scores of PAE and OMD mice were significantly lower compared to their respective controls (PAE vs. PAE-control, P = 0.0045; OMD vs. OMD-control, P = 0.035; two-tailed Student’s t-test). Statistical tests: Two-way repeated measures ANOVA (C–H) followed by the post hoc simple main effect test (D and H). Sample sizes (# mice): (C–H) MD-control = 3, MD = 4; (J and K) PAE-control = 37, PAE = 41, OMD-control = 30, OMD = 26. (C–H and J) Line graphs represent mean ± SEM. * = significantly different with P-values of *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.