Iron Deprivation during Fetal Development Changes the Behavior of Juvenile Rhesus Monkeys2

Abstract

Sensitive periods for induction of behavioral impairments by developmental iron deficiency were studied in a nonhuman primate model. Rhesus monkey infants were deprived of iron prenatally (n = 14) via the dam's diet (10 microg Fe/g) or postnatally (birth-4 mo, n = 12) via infant formula (1.5 mg Fe/L). They were compared with controls (n = 12) with adequate dietary iron throughout development in a series of cognitive tests and related assessments from 6 to 12 mo of age, a developmental stage corresponding approximately to 2-4 y of age in humans. Health, growth, and hematological status were not affected. Auditory brainstem response and white matter volumes in the cerebrum were similarly unaffected. Male infants in the prenatally deprived group had reduced spontaneous daytime activity relative to controls, as monitored by actimeter. On cognitive tests, prenatally deprived juveniles had similar level of correct responding, but showed more completed trials, and shorter latencies during early phases of the tests. Juveniles deprived of iron as infants showed a similar pattern of behavioral change, but most differences from controls were not as great. Inadequate iron nutrition during pregnancy was reflected in the juvenile period primarily as attenuated inhibitory response. This finding may be relevant to individual differences in temperament or to behavior disorders in children involving reduced inhibitory control.

Developmental plasticity of red blood cell homeostasis

“…We first investigated RBC dynamics in a nonhuman primate model, rhesus macaques, where third trimester iron deficiency is induced by a low iron diet [19, 24, 28]. In utero dietary iron deprivation (ID) was comparable to the 25 th percentile of iron intake among pregnant US women [19], and thus represents a very mild perturbation which was not expected a priori to have an observable effect on infant hematology.…”

Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

“…Early brain-wide ID leads to impairments of learning and memory, mood and affect, and speed of processing through its effects on the hippocampus, on monoamine-rich areas like the striatum and on myelin. All three processes are undergoing rapid development in the late fetal and early neonatal period (Thompson and Nelson 2001; Georgieff and Innis 2005; Ward et al 2007), but fetal ID tends to compromise the hippocampus disproportionately (deUngria et al 2000; Golub et al 2007) resulting in long term spatial learning and memory abnormalities (Schmidt et al 2007). However, prior models that induced pan-brain ID were unable to provide any understanding of the relative contributions of the three processes to altered behavioral function during ID.…”

Neural Correlates of Emotion Processing in Typically Developing Children and Children of Diabetic Mothers

“…The amygdala, therefore, is likely to be a structure impacted by perinatal iron deficiency at some level, with adverse consequences for the processing of the emotional value of a stimulus. Golub and colleagues (2007), for instance, found that prenatally iron-deprived juvenile Rhesus monkeys demonstrated less behavioral inhibition in new and challenging environments than did controls, suggesting the absence (or at least a reduction) in the expression of negative emotions (i.e., fear and anxiety); emotions that are normally expressed in encounters with novel objects or environments but which can be disrupted by damage to the amygdala (Izquierdo, Suda, & Murray, 2005; Mason, Capitanio, Machado, Mendoza, & Amaral, 2006). Thus, group differences in the processing of emotional signal values may reflect, in part, alterations in amygdala function and connections between the amygdala and the neocortex, in addition to deviations in the development of memory-related neural circuitry.…”