An endophenotype of the fetal alcohol effect on POMC gene is the hyperresponse of the HPA axis to stress [4], [5], [8]. We hypothesized that the MeCP2 normalizing effect on POMC gene expression would be reflected in the HPA axis response to an immune challenge. Previously, we have shown that fetal alcohol exposure increases CRH levels in the MBH and increases plasma ACTH and corticosterone responses to an LPS challenge [21]. In agreement with our previous study, we show here that fetal alcohol exposure increased CRH levels in the MBH (Fig. 5A) and increased plasma levels of ACTH and corticosterone 2 h after an LPS injection relative to control scr shRNA treated rats (Fig. 5B, C). In addition, we show here MeCP2 shRNA treatment prevented fetal alcohol effect on hypothalamic CRH and plasma ACTH and corticosterone response to LPS challenge. These results suggest that MeCP2 plays an important role in fetal alcohol-induced suppression of POMC gene expression and its control of the HPA axis function.
