Common behavioral influences of the ErbB1 ligands transforming growth factor alpha and epiregulin administered to mouse neonates

Ligands for epidermal growth factor (EGF) receptor (ErbB1), such as EGF, transforming growth factor alpha (TGFα), and epiregulin, are enriched in body fluids and blood and regulate development of various peripheral organs. It remains however how such circulating polypeptide growth factors influence brain development and function. Here, we performed peripheral injections of TGFα and epiregulin to mouse neonates and evaluated immediate physical and neurochemical development and later behavioral consequences. Subcutaneous administration of TGFα and epiregulin increased phosphorylation of brain ErbB1, suggesting their effects on brain development. Repeated their injections similarly enhanced physical development of eyelid opening and tooth eruption during early postnatal stage and resulted in abnormal behavioral traits in the adult stage. Acoustic startle responses of mice treated with these growth factors as neonates were enhanced and prepulse inhibition was decreased without an apparent correlation between prepulse inhibition level and startle intensity. Locomotor activity and fear-learning performance with tone and context cues were not altered, however. These results suggest that circulating ErbB1 ligands in the periphery of neonates have some common influences on later behavioral traits. Abnormal ErbB1 ligand production at neonatal and potentially prenatal stages might therefore associate with neurodevelopmental disorders such as schizophrenia.