Evidence for an immune signature of prenatal alcohol exposure in female rats

Brain Behav Immun. 2016 Nov;58:130-141. doi: 10.1016/j.bbi.2016.05.022. Epub 2016 Jun 2.


Evidence for immune/neuroimmune disturbances as a possible root cause of a range of disorders, including neurodevelopmental disorders, is growing. Although prenatal alcohol exposure (PAE) impacts immune function, few studies to date have examined immune function in relation to long-term negative health outcomes following PAE, and most have focused on males. To fill this gap, we utilized a rat model to examine the effects of PAE on immune/neuroimmune function during early-life [postnatal day 1 (P1), P8, and P22] in PAE and control females. Due to the extensive interplay between the immune and endocrine systems, we also measured levels of corticosterone and corticosterone binding globulin (CBG). While corticosterone levels were not different among groups, CBG levels were lower in PAE offspring from P1 to P8, suggesting a lower corticosterone reservoir that may underlie susceptibility to inflammation. Spleen weights were increased in PAE rats on P22, a marker of altered immune function. Moreover, we detected a unique cytokine profile in PAE compared to control offspring on P8 - higher levels in the PFC and hippocampus, and lower levels in the hypothalamus and spleen. The finding of a specific immune signature in PAE offspring during a sensitive developmental period has important implications for understanding the basis of long-term immune alterations and health outcomes in children with Fetal Alcohol Spectrum Disorder (FASD). Our findings also highlight the future possibility that immune-based intervention strategies could be considered as an adjunctive novel therapeutic approach for individuals with FASD.

Keywords: Brain; Corticosteroid binding globulin (CBG); Cytokines; Fetal Alcohol Spectrum Disorder (FASD); Prenatal alcohol exposure; Spleen.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / immunology*
  • Brain / metabolism
  • Brain / pathology
  • C-Reactive Protein / metabolism
  • Corticosterone / blood
  • Cytokines / blood
  • Cytokines / metabolism
  • Ethanol / administration & dosage*
  • Female
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects / immunology*
  • Prenatal Exposure Delayed Effects / metabolism
  • Rats, Sprague-Dawley
  • Sex Characteristics*
  • Spleen / drug effects
  • Spleen / immunology*
  • Spleen / metabolism
  • Spleen / pathology


  • Cytokines
  • Ethanol
  • C-Reactive Protein
  • Corticosterone