The Role of Prostaglandin E2 in the Expression of Hemoglobin During Prenatal and Postnatal Brain Development - Potential Connection to Autism Spectrum Disorders

Abnormal levels of the fetal hemoglobin isoform Hbb- and the adult isoforms Hbb- and Hba- have been found in the prenatal male brain of our mouse model lacking prostaglandin E2 (PGE2) producing enzyme cyclooxygenase-2 (COX2-knockout). Dysregulations of the COX2/PGE2 pathway has also been linked to autism. In this study, we use quantitative Real-Time PCR, western blots, and immunohistochemistry to investigate the expression of Hba-, Hbb-, and Hbb- in the brain of COX2-knockin (COX2-KI) mice. Overall, gene expression was affected in a sex-dependent manner and by deficits of the COX2/PGE2 pathway. Protein expression analysis also revealed sex-dependent changes and differences for the COX2-KI animals. Interestingly, regional expression analysis showed a distinct pattern of Hbb- in the white matter, whereas Hba- and Hbb- were expressed in the grey matter. These results add new knowledge about the involvement of COX2/PGE2 pathway in the regulation of hemoglobin in the brain with implications for autism.