Novel peptides prevent alcohol-induced spatial learning deficits and proinflammatory cytokine release in a mouse model of fetal alcohol syndrome

Objective: Previously, the novel peptides NAPVSIPQ and SALLRSIPA were shown to prevent alcohol-induced fetal death and growth abnormalities in a mouse model of fetal alcohol syndrome. This study evaluated whether these peptides could prevent long-term alcohol-induced learning abnormalities. In addition, because specific cytokines are known to effect long-term potentiation, a model of learning at the molecular level, we studied the effect of these novel peptides on tumor necrosis factor-alpha, interleukin-6, and interferon-gamma levels. Study design: We used a well-characterized mouse model of fetal alcohol syndrome. Pregnant mice were injected on day 8 with alcohol (0.03 mL/kg) or placebo. Pretreatment with NAPVSIPQ + SALLRSIPA (20 mu g) or placebo was given 30 minutes before alcohol. Embryos were removed after 6 hours, at which time cytokine, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma levels were measured with enzyme-linked immunoassays. To test spatial learning, adult offspring from litters that were treated with alcohol, control, NAPVSIPQ + SALLRSIPA then alcohol, or NAPVSIPQ + SALLRSIPA alone were evaluated for latency to find a hidden platform in the Morris water maze. Results: Alcohol treatment increased tumor necrosis factor-alpha levels versus control levels (50.0 +/- 3.5 pg/mL vs 32.7 +/- 2.4 pg/mL; P <= .001). NAPVSIPQ + SALLRSIPA pretreatment prevented this increase (39.9 9 +/- 2.8 pg/mL; P < .01), with levels similar to control (P = .1). Similarly, alcohol increased interleukin-6 levels versus control levels (22.6 +/- 1.4 pg/mL vs 17.3 +/- 0.6 pg/mL; P < .001), and NAPVSIPQ + SALLRSIPA prevented this increase (19.1 +/- 1.0 pg/mL; P < .02), with levels similar to control levels (P = .2). Interferon-gamma levels were not different among the 3 groups (alcohol, 14.6 + 4.9 pg/mL; control, 17.9 +/- 6.6 pg/mL; alcohol + NAPVSIPQ + SALLRSIPA, 13.6 +/- 4.9 pg/mL; P = .2). In the Morris water maze, alcohol-treated groups did not learn over the 7-day trial compared with the control group (P = .001). Groups that were pretreated with NAPVSIPQ + SALLRSIPA then alcohol learned significantly, which was similar to the control group. Groups that were treated with only NAPVSIPQ + SALLRSIPA learned significantly earlier, with the shortest latency once learning commenced.