EFFECTS OF REPEATED ADMINISTRATIONS OF EGF AND TGF-ALPHA ON MOUSE NEUROBEHAVIORAL DEVELOPMENT

In this study we tested the effects of repeated administrations of Epi dermal Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-a lpha) on mouse pups' neurobehavioral development. Each subject was inj ected subcutaneously with either EGF or TGF-alpha on postnatal days 2, 4, 6, 8, and 10. Pups treated with these two peptides showed accelera ted eyelid opening and eruption of the lower incisors when compared to Cytochrome c-injected control littermates. EGF, but not TGF-alpha res ulted in a slight body growth retardation. When scored for a number of neurobehavioral parameters, EGF pups showed a delayed appearance of t he righting reflex. Also, EGF-treated pups exhibited greater ultrasoni c vocalization calling rates than controls when tested on postnatal da y 7. Overall, TGF-alpha administration resulted in minor effects, when compared with EGF treatment, probably as a result of the lower dose a dministered (EGF: 3.5 mg/kg vs TGF-alpha :1 mg/kg). TGF-alpha affected pups' eyelid opening and incisor eruption, similarly to EGF, but seem ed to exert an opposite effect on some neurobehavioral scores, in line with what was already reported for Nerve Growth Factor (NGF) (Calaman drei and Alleva, 1989). These results confirm the role played by polyp eptide growth factors on mammalian physical and neurobehavioral develo pment and suggest that TGF-alpha might affect mouse brain development in a similar fashion as NGF. (C) 1994 Intox Press, Inc.