53: Neuroprotective fractalkine in fetal alcohol syndrome

Abstract

Fetal alcohol syndrome (FAS) is associated with mental retardation and neurodevelopmental abnormalities. Neuroprotective peptides (NAP+SAL) can prevent some of the alcohol-induced damage in FAS including fetal death, growth abnormalities and learning impairment. Fractalkine, a chemokine constitutively expressed in neurons throughout the CNS, has a role in neuroprotection reducing neuronal death from activated microglia. Using a model of FAS we evaluated if fractalkine is altered in FAS and if the neuroprotective peptides NAP+SAL work through preventing alterations in fractalkine. Using a well-characterized FAS model, timed, pregnant C57BL6/J mice were treated on gestational day 8 (E8) with alcohol (0.03 mL/g), placebo or alcohol+peptides. Embryos were harvested 24h later on gestational day 9 and 10 days later at E18. Fractalkine was measured using a microsphere-based multiplex immunoassay (Luminex xMAP, Millipore, MA). Statistical analysis included Kruskal-Wallis with P<.05 significant. Six hours after alcohol exposure, fractalkine levels were signficantly elevated(median 341pg/ml, range 263-424pg/ml) vs controls (median 228pg/ml, range 146-332pg/ml; P<.001; Figure). Embryos treated with alcohol and the peptides NAP+SAL prevented the alcohol induced increase in fractalkine (median 137, range 97-255 pg/ml, P<.001). At E18 (10d after exposure), fractalkine levels were similar in all groups (medians 1821, 1852 and 2013 pg/ml respectively, P=0.7). Prenatal alcohol exposure acutely results in elevation of the neuroprotective chemokine fractalkine, perhaps in an effort to counter the alcohol toxicity. Treatment with the peptides NAP+SAL along with the alcohol prevents the acute increase in fractalkine.