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Moderate Copper Deprivation during Gestation and Lactation Affects Dentate Gyrus and Hippocampal Maturation in Immature Male Rats^1,2,

United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202

The hippocampal formation (HF) is involved in higher brain functions including learning and declarative memory. The possibility that dietary copper has a role in the morphological development, and therefore the function of the HF, has received little attention. A rat model of tiered copper deficiency, initiated during gestation, was employed to determine the susceptibility of the HF, regions of which develop postnatally, to copper deficiency. At postnatal 23, pups whose dams had received either 1.8 or 1.4 mg Cu/kg diet during both gestation and lactation, compared with offspring of a group that had received 4.3 mg Cu/kg diet during both periods had, significantly more cell nuclei in the infrapyrimidal arm of the dentate gyrus. Offspring of rats fed 1.4 mg Cu/kg diet, but not those fed 1.8 mg/kg, compared with those fed 4.3 mg/kg, exhibited smaller, shorter, and narrower cell nuclei in the infrapyrimidal and suprapyrimidal arms of the dentate gyrus and smaller cell nuclei in region CA3c of the hippocampus. A fourth group (gestation, 1.8 mg Cu/kg diet; lactation, 0.9 mg Cu/kg diet) exhibited alterations less marked than those exhibited by the group fed 1.4 mg Cu/kg diet. All alterations in the groups fed low copper diets were consistent with slowed cell nuclear maturation. The findings indicate that copper is required for maturation of the dentate gyrus and hippocampus. Also, copper supplied at or below 1.8 mg/kg is insufficient for morphological maturation of the dentate gyrus and hippocampus. Because the HF is important for higher brain functions, further research is needed to determine whether the copper deficiency-induced alterations in dentate gyrus and hippocampus development are transient or permanent.

KEY WORDS: • copper deficiency • hippocampus • granule cell • pyramidal cell • rats

¹ U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area is an equal opportunity/affirmative action employer and all agency services are available without discrimination.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 20 October 1994. Revision accepted 5 June 1995.