Neurobehavioral evaluation of rhesus monkey infants fed cow's milk formula, soy formula, or soy formula with added manganese

Golub, Mari S.; Hogrefe, Casey E.; Germann, Stacey L.; Tran, Trinh T.; Beard, John L.; Crinella, Francis M.; Lönnerdal, Bo

doi:10.1016/j.ntt.2005.04.003

Cited by 115 publications

(93 citation statements)

References 34 publications

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“…Given the risk posed by high Mn concentrations in infant formulas (Golub et al, 2005) their composition has significantly changed over the last 20 years. For example, Enfamil (Mead Johnson and Company) contained 1289 μg Mn/L in 1983; levels dropped to 105 μg/L shortly thereafter .…”

Section: Milk and Infant Formulasmentioning

confidence: 99%

Manganese neurotoxicity: A focus on the neonate

Erikson

Thompson

Aschner

et al. 2007

Pharmacology & Therapeutics

221

141

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Manganese (Mn) is an essential trace metal found in all tissues, and it is required for normal amino acid, lipid, protein, and carbohydrate metabolism. While Mn deficiency is extremely rare in humans, toxicity due to overexposure of Mn is more prevalent. The brain appears to be especially vulnerable. Mn neurotoxicity is most commonly associated with occupational exposure to aerosols or dusts that contain extremely high levels (> 1-5 mg Mn/m 3 ) of Mn, consumption of contaminated well water, or parenteral nutrition therapy in patients with liver disease or immature hepatic functioning such as the neonate. This review will focus primarily on the neurotoxicity of Mn in the neonate. We will discuss putative transporters of the metal in the neonatal brain and then focus on the implications of high Mn exposure to the neonate focusing on typical exposure modes (e.g., dietary and parenteral). Although Mn exposure via parenteral nutrition is uncommon in adults, in premature infants, it is more prevalent, so this mode of exposure becomes salient in this population. We will briefly review some of the mechanisms of Mn neurotoxicity and conclude with a discussion of ripe areas for research in this underreported area of neurotoxicity.

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Section: Milk and Infant Formulasmentioning

confidence: 99%

Manganese neurotoxicity: A focus on the neonate

Erikson

Thompson

Aschner

et al. 2007

Pharmacology & Therapeutics

221

141

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“…These infants were offspring of dams fed iron-regulated purified diets during pregnancy, either 10 μg Fe/g (iron deprived) or 100 μg Fe/g (iron adequate) [27]. Iron status of the dams during pregnancy and of the infants at birth have been previously reported [26].…”

Section: Subjectsmentioning

confidence: 99%

“…CNPRC maintains nonhuman primate nurseries housing approximately 200 infants each year using standard protocols that have been found to optimize infant well-being as described previously [27]. Neonates were first housed in heated incubators then transitioned to social housing in small metal cages.…”

Section: Animal Housing and Carementioning

confidence: 99%

“…Weekly 10-min sessions were conducted in a specialized cage (38 × 38 × 86 cm) with plastic mesh sides that allowed climbing [17,27,21,22,23,19]. Infant behavior initiations were recorded for a 7.5 min session after a 2.5 min acclimation period using a checklist of exhaustive, mutually exclusive categories that included mature and immature forms of motor behaviors (sitting, stand, walk, climb up, climb down, cage manipulation) [17].…”

Section: Motor and Postural Maturationmentioning

confidence: 99%

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Behavioral consequences of developmental iron deficiency in infant rhesus monkeys

Golub

Hogrefe

Germann

et al. 2006

Neurotoxicology and Teratology

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Human studies have shown that iron deficiency and iron deficiency anemia in infants are associated with behavioral impairment, but the periods of brain development most susceptible to iron deficiency have not been established. In the present study, rhesus monkeys were deprived of iron by dietary iron restriction during prenatal (n = 14, 10 μg Fe/g diet) or early postnatal (n = 12, 1.5 mg Fe/L formula) brain development and compared to controls (n = 12, 100 μg Fe/g diet, 12 mg Fe/L formula) in behavioral evaluations conducted during the first four months of life in the nonhuman primate nursery. Iron deficiency anemia was detected in the pregnant dams in the third trimester and compromised iron status was seen in the prenatally iron-deprived infants at birth, but no iron deficiency was seen in either the prenatally or postnatally iron-deprived infants during the period of behavioral evaluation. Neither prenatal nor postnatal iron deprivation led to significant delays in growth, or gross or fine motor development. Prenatally deprived infants demonstrated a 20% reduced spontaneous activity level, lower inhibitory response to novel environments, and more changes from one behavior to another in weekly observation sessions. Postnatally deprived infants demonstrated poorer performance of an object concept task, and greater emotionality relative to controls. This study indicates that different syndromes of behavioral effects are associated with prenatal and postnatal iron deprivation in rhesus monkey infants and that these effects can occur in the absence of concurrent iron deficiency as reflected in hematological measures.

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“…Likewise, infant rhesus monkeys fed soy formula containing Mn chloride performed no differently than controls on complex learning tasks (e.g., delayed nonmatch to sample, continuous performance test, etc.) (Golub et al, 2005). In adult rats, unlearned locomotor responding is often disrupted by perturbations of the nigrostriatal and mesocorticolimbic dopamine systems, therefore it is surprising that Mn has been reported to increase (Nachtman et al, 1986;Calabresi et al, 2001), decrease (Ingersoll et al, 1995;Talavera et al, 1999), or have no effect (Dorman et al, 2000;Reichel et al, 2006) on spontaneous locomotor activity.…”

Section: Introductionmentioning

confidence: 99%

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

McDougall¹,

Reichel²,

Farley³

et al. 2008

Neuroscience

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In the present study, we examined whether exposing rats to a high-dose regimen of manganese chloride (Mn) during the postnatal period would depress presynaptic dopamine functioning and alter nonassociative and associative behaviors. To this end, rats were given oral supplements of Mn (750 μg/day) on postnatal days (PD) 1-21. On PD 90, dopamine transporter (DAT) immunoreactivity and [ 3 H]dopamine uptake were assayed in the striatum and nucleus accumbens, while in vivo microdialysis was used to measure dopamine efflux in the same brain regions. The effects of postnatal Mn exposure on nigrostriatal functioning were evaluated by assessing rotorod performance and amphetamine-induced stereotypy in adulthood. In terms of associative processes, both cocaineinduced conditioned place preference (CPP) and sucrose-reinforced operant responding were examined. Results showed that postnatal Mn exposure caused persistent declines in DAT protein expression and [ 3 H]dopamine uptake in the striatum and nucleus accumbens, as well as long-term reductions in striatal dopamine efflux. Rotorod performance did not differ according to exposure condition, however Mn-exposed rats did exhibit substantially more amphetamine-induced stereotypy than vehicle controls. Mn exposure did not alter performance on any aspect of the CPP task (preference, extinction, or reinstatement testing), nor did Mn affect progressive ratio responding (a measure of motivation). Interestingly, acquisition of a fixed ratio task was impaired in Mn-exposed rats, suggesting a deficit in procedural learning. In sum, these results indicate that postnatal Mn exposure causes persistent declines in various indices of presynaptic dopaminergic functioning. Mninduced alterations in striatal functioning may have long-term impact on associative and nonassociative behavior.

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Neurobehavioral evaluation of rhesus monkey infants fed cow's milk formula, soy formula, or soy formula with added manganese

Cited by 115 publications

References 34 publications

Manganese neurotoxicity: A focus on the neonate

Manganese neurotoxicity: A focus on the neonate

Behavioral consequences of developmental iron deficiency in infant rhesus monkeys

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

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