Project II (Davis monkey) will determine the immediate and long-term effects of prenatal iron deficiency in infant monkeys. The last project period aimed to identify susceptibility of two different periods of brain development to iron deficiency in rhesus monkeys, (1) the proliferation and growth phase of brain development, which takes place primarily in the third trimester in primates, and (2) the period of regional diversification and interconnection that occurs later in infancy. Two different patterns of long-lasting behavioral consequences were identified when iron deprivation was limited by experimental protocol to one of these two periods;iron deprivation during the earlier period led to a syndrome of impulsiveness and lower environment-induced behavioral inhibition, while deprivation during the second period led to a syndrome of heightened emotionality and cognitive delay. The data suggest a pattern of infant behavior in prenatally deprived infants that may progress to impairments relevant to dopamine system functions and childhood disorders involving impulse control. This hypothesis will be examined in the current project period through followup of prenatally iron deprived infants through two years of age, approximately equivalent to eight years in children, with an emphasis on tests of impulsivity and social conduct, and response to dopamine-active pharmacological agents. PET imaging will be used to assess brain mesolimbic dopamine systems, in parallel to methods used in children. The findings on time-dependent effects of iron deprivation also suggest that prenatal iron deficiency can impact the function of neonates, requiring correction by supplementation at earlier ages than are typically used in human infants. This hypothesis will be tested through evaluation of physiological regulation (wakesleep, body temperature, heart rate variability) and early motor development and cognitive function (taste recognition). Possible adaptive and compensatory changes at the cellular level will be assessed with proteomic profiles of white blood cells at birth. Both arms of PPG2's Project II have immediate relevance to human problems. Identifying effects of prenatal iron deficiency at the equivalent of the school-aged child may help anticipate later problems in the thousands, if not millions, of children worldwide who experience prental iron deficiency. In-depth assessment of effects in the newborn may point to early behavioral alterations that foreshadow long-term consequences. If these can be recognized, infants might be identified at younger ages and receive appropriate intervention.
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