Postnatal decrease in transforming growth factor alpha is associated with enlarged ventricles, deficient amygdaloid vasculature and performance deficits

It is well established that transforming growth factor or is involved prena tally in development of the nervous system, but its role in the postnatal b rain is less well understood. Here, we document the occurrence of late-onse t morphological and behavioral deficits in the naturally occurring murine m utant, Waved-1 (Wa-1), whose transforming growth factor alpha levels decrea se naturally between early postnatal and adolescent ages. Morphological ana lyses suggest that reduction in the growth factor postnatally is associated temporally with the onset of enlarged lateral ventricles, a reduction in v asculature in the region of the amygdala and a reduction in size of the cen tral nucleus. Onset of the morphological deficits corresponds to the appear ance of a performance deficit in contextual fear conditioning. In contrast, the transforming growth factor alpha gene-targeted null mutants exhibit ne ither morphological nor performance deficits. These data suggest that transforming growth factor alpha during postnatal m aturation of the brain may contribute to maintenance of limbic morphology a nd vasculature, which may in turn affect some behaviors associated with the se specific brain structures. (C) 2000 IBRO. Published by Elsevier Science Ltd.