Iron deficiency and neurotransmitter synthesis and function

There has been little work on the effects of irondeficiency on brain metabolism and function despite the fact that Fe deficiency is the most common nutritional disorder in the world (Garby, 1973; Kossner 8z Kalk, 1973). Fe is present in the brain in relatively large amounts and is particularly concentrated in the basal ganglia (Cumings, 1948, 1968; Hallgren 8z Sourander, 1958; Harrison, Netsky 8z Brown, 1968). Furthermore it’s concentration appears to be independent of the liver Fe stores (Hallgren 8z Sourander, 1958; Dallman, 1974). It has been suggested that Fe is a cofactor for tyrosine hydroxylase (EC 1.14.16.2) (Sourkes, 1972) and tryptophan hydroxylase (EC 1.13.11.11) (Ichiyama, Nakamura, Nishizuka 8z Hayashi, 1968; Lovenberg, Jequier & Sjoerdsma, 1968; Youdim, Hamon 8z Bourgoin, 1975), enzymes involved in the formation of catecholamines and 5-hydroxytryptamine (5-HT) respectively. The activity of the monoamine degradative enzyme monoamine oxidase (EC 1.4.3.4; MAO) has also been shown to be lowered in the tissues of both humans and rats with Fedeficiency anaemia (Symes, Sourkes, Youdim, Birnbaum & Gregoriadis, 1969; Voorhess, Stuart, Stockman 8z Oski, 1975; Youdim, Woods, Mitchell, GrahameSmith 8z Callender, 1975; Youdim, Grahame-Smith 8z Woods, 1976). We have now investigated the effects of Fe deficiency in rats on the activity of various monoamine-metabolizing enzymes in the brain. The functional activity of the monoamine neurotransmitter systems has also been investigated by measuring the behavioural responses of the rats to increased brain 5-HT and dopamine (DA) receptor stimulation. Preparation of Fe-dejcient rats Male Sprague-Dawley rats (Anglia Laboratory Animals, Huntingdon), initial weight 80+20 g (meanksm) were made Fe deficient by feeding on a semisynthetic diet of milk powder low in Fe (McCall, Newman, O’Brien, Valberg & Witts, 1962) and distilled water. Control rats were given tapwater and the milkpowder diet with ammonium ferrous sulphate (1.3 mg/g diet) added. The Fedeficient group were given ad lib. access to the diet while the control group had their food intake restricted to that of the Fe-deficient group. After 5 weeks the