Marginally low copper causes lesions of the midbrain in animal models: the implications for man

Serum copper levels must be maintained between very strict limits for the maintenance of good health. High levels have recently been linked to Alzheimer's disease while low levels during pregnancy cause enzootic ataxia (swayback disease) in offspring. In this study, we investigated the prolonged effect of serum copper that was maintained at and around 0.5 ppm, the level presently regarded as safe. Pregnant sheep and rabbits in the last trimester (1-4 weeks) of pregnancy were treated with the copper chelator ammonium tetrathiomolybdate (ATM). Treatment was continued until the young were one month old at which time the animals were sacrificed Serum copper levels of the parents and offspring were monitored by atomic absorption. The difference spectra (400-630 nm) was examined and SDS PAGE was used to evaluate the protein composition of the brain mitochondria. The anatomy of the midbrain was also studied. Although the young sheep and rabbits from the ATM-treated mothers showed no visible signs of disability or swayback disease, the midbrain of those young animals with serum copper between 0.3-0.9 ppm showed evidence of vacuolation, cavitation and chromatolysis. In contrast, the difference spectra and the protein composition of the brain mitochondria from these animals were all normal. These results suggest that although animals may appear normal and exhibit some normal biochemical markers, serum copper in the region of 0.5 ppm may not be safe for some breeds of sheep or rabbits. It is possible that a similar situation applies to man. Los niveles sericos cupricos tienen que ser mantenidos dentro de limites muy estrictos, si se quiere tener una buena salud. Los altos niveles de cobre han sido asociados recientemente con la enfermedad de Alzheimer, mientras que los niveles bajos durante el embarazo causan ataxia enzootica (swayback) enla descendencia. En este estudio investigamos el efecto prolongado del cobre serico mantenido a 0.5 ppm o alrededor de 0.5 ppm – el nivel considerado seguro actualmente. Ovejas y conejas prenadas, en el ultimo trimestre (1-4 semanas) de gestacion, fueron tratadas con el quelante del cobre conocido como tetratiomolibdato de amonio (TM). El tratamiento continuo hasta que las crias tuvieron un mes,momento en el que los animales fueron sacrificados. Los niveles sericos cupricos de los progenitores y la progenie fueron monitoreados mediante absorcion atomica. Se examinaron los espectros de diferencia (400– 630 nm). Se uso la tecnica de SDS-PAGE para evaluar la composicion proteica de lasmitocondrias cerebrales. Tambien se estudio la anatomia del mesencefalo. Aunque la anatomia de las crias de ovejas y conejas madres tratadas con TM no mostraron senales visibles de discapacidad o enfermedad swayback, el mesencefalo de estas crias con cobre serico entre 0.3–0.9 ppm, mostroevidencias de vacuolacion, cavitacion y cromatolisis. En contraste con ello, los espectros de diferencia y la composicion proteica de las mitocondrias del cerebro de estos animales, fueron todos normales. Estos resultados sugieren que aunque los animales puedan parecer normales y presentar marcas bioquimicas normales, el cobre serico en el rango de 0.5 ppm, puede no ser seguro para algunas crias de ovejas y conejos. Es posible que una situacion similar se aplique al ser humano.