Long-term consequence of early iron-deficiency on dopaminergic neurotransmission in rats.
Nutritional iron-deficiency (ID) induced in rats caused a reduction in peripheral as well as central iron metabolism. This effect was markedly greater in the liver than the brain. Although the decrease in the rate of brain non-haem iron was slower than that of serum and liver, significant diminutions of behavioral response to apomorphine (2 mg/kg) and maximum [3H]spiperone binding (Bmax) in caudate nucleus were noted in these animals. These effects of ID can be reserved by iron supplementation in young (21-day-old) and adult (48-day-old) rats. In contrast, if ID is induced in new born (10-day-old) animals, the diminished brain non-haem iron, behavioral response to apomorphine and [3H]-spiperone binding in caudate nucleus will not recover even after 6 weeks of iron supplementation. However, these animals have normal serum iron, haemoglobin and liver iron. These data point to the profound effect early ID can have on the development of dopaminergic neurotransmission, since brain iron concentration increases its maximum in the 4-5 weeks after birth. The implications of the present finding is that the prevalence of ID in children occurs in the first decade of life, when brain iron accumulation reaches values observed in adults. The profound cognitive changes associated with ID in children is thought to be dopamine-dependent and is not always reversible with iron therapy.
Ben-Shachar
D
D
Rappaport Family Institute for Medical Research, Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel.
Ashkenazi
R
R
Youdim
M B
MB
D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001058:Apomorphine / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D007501:Iron / Q000502:physiology; D000090463:Iron Deficiencies; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D009435:Synaptic Transmission; D013997:Time Factors
D011954:Receptors, Dopamine; D013134:Spiperone; D007501:Iron; D001058:Apomorphine; D004298:Dopamine