ARS | Publication request: Abnormal Motor Function Persists Following Recovery from Perinatal Copper Deficiency in Rats

Submitted to: Journal Of Nutrition
Publication Acceptance Date: May 20, 2004
Publication Date: August 1, 2004
Citation: Penland, J.G., Prohaska, J.R. 2004. Abnormal Motor Function Persists Following Recovery From Perinatal Copper Deficiency In Rats. Journal Of Nutrition. 134(8):1984-1988.

Interpretive Summary: There is increasing evidence that copper is important for brain development and function, and it is likely that both the degree and timing of inadequate copper intakes determine long-term impact. This study examined the long-term biochemical and behavioral consequences of perinatal copper deficiency in Holtzman rats. Pregnant females were fed a diet low in copper (0.34 mg Cu/kg diet) from gestation day 7 through lactation day 21. At weaning, male offspring were switched to a nonpurified copper-adequate diet and biochemical and behavioral assessments were done after approximately 3 and 6 months. Compared to controls, copper-repleted rats had lower brain copper and iron levels following both 3 and 6 months of repletion; other biochemical differences were not detected. Behavioral assessments found a persistent impairment in motor function of copper-repleted compared to control rats when evaluated by the accelerating rotorod procedure. However, measurements of other aspects of behavior, such as startle responses, locomotor activity, emotionality and memory, were not significantly different between copper-repleted and control rats. Findings indicate that inadequate copper intakes during early development can result in relatively permanent changes in motor function, and underscore the importance of ensuring adequate copper intakes throughout pregnancy and early development.

Technical Abstract: What are the biochemical and behavioral consequences of perinatal copper deficiency? Pregnant Holtzman rats were fed a modified AIN-86A diet low in copper (0.34 mg Cu/kg and 42 mg Fe/kg) starting on gestation day 7. Seven rats received copper in their drinking water (20 mg Cu/L) (+Cu) and 7 drank dionized water (-Cu). Treatments did not affect litter size or pregnancy outcome. Compared to +Cu dams and a sample of +Cu male weanling (P21) offspring, -Cu rats exhibited signs consistent with copper deficiency. P21 males were switched to a nonpurified copper adequate diet and sampled biochemically after 3 months and behaviorly after 3 and 6 months of repletion (CuR). Compared to controls, CuR rats had lower brain copper and iron levels 3 and 6 months after repletion, other biochemical differences were not detected. Behavioral assessments after 5 months of repletion found a persistent impairment in motor function of CuR compared to control rats as evaluated by the accelerating rotorod procedure. These results suggest that permanent impairment to motor function can persist following long-term recovery from perinatal copper deficiency.