Recent studies of iron deficiency during brain development in nonhuman primates

Abstract

Recent studies of the effects of developmental iron deficiency and iron deficiency anemia in nonhuman primates have provided new insights into this widespread and well-recognized human nutritional deficiency. The rhesus monkey was the animal model in these experiments which used extensive hematological and behavioral evaluations in addition to noninvasive brain measures. Two important findings were (1) different behavioral consequences depending on the timing of iron deficiency relative to brain developmental stages, and (2) the potential for long lasting changes in brain iron regulatory systems. Further work in this model, including integration with studies in humans and in laboratory rodents, is ongoing.

Quantitative Proteomic Analyses of Cerebrospinal Fluid Using iTRAQ in a Primate Model of Iron Deficiency Anemia

“…In nonhuman primates, the timing of the iron deficiency insult has also been shown to be critical to the development of certain behaviors. Prenatal iron deficiency led to increased impulsive behavior, whereas postnatal iron deficiency resulted in more passive behavior [43]. Monkeys that experience IDA during development perform also more poorly on a cognition test (reversal learning) even after the systemic ID has been corrected [44] consistent with the current report of prolonged alterations in CSF proteome.…”

Long-term brain and behavioral consequences of early iron deficiency

“…Long‐term behavioral effects include less exploration and fear of novel situations, findings that map well onto similar behaviors in the human (see above) 41 . Non‐human primate models, in which more human‐like behaviors can be assessed, show that prenatal ID leads to more impulsive behavior while postnatal IDA results in more passive, withdrawn behavior that is reminiscent of the findings in humans 42 …”

“…41 Non-human primate models, in which more humanlike behaviors can be assessed, show that prenatal ID leads to more impulsive behavior while postnatal IDA results in more passive, withdrawn behavior that is reminiscent of the findings in humans. 42 Myelin synthesis is dependent on iron for a number of defined and, likely, several as yet undefined mechanisms. Myelin is synthesized by oligodendrocytes and begins prenatally in rodents and humans.…”

Iron function and dysfunction in the brain: A pediatric neurologist's perspective

“…Animal models, such as rodents and nonhuman primates, confirm that iron deficiency is associated with cognitive abnormalities. Experimental models also allow more detailed behavioral, metabolic, and structural analyses than are possible in patients [62]. In animals, iron deficiency or other nutritional perturbations can be initiated at specific time points during development, to determine the most vulnerable ages and brain regions; duration of iron deficiency can be varied and outcomes measured at later time points.…”