The effects of iron deficiency on brain biogenic monoamine biochemistry and function in rats

Abstract

Rats were made iron-deficient by feeding them on a semi-synthetic diet containing milk powder, low in iron. Control rats were fed the same diet with an iron-supplement. When the rats were iron deficient (haemoglobin 6.9 ± 0.6 g/ dl) a study was made of the iron distribution in the brain. Distribution was similar in control and iron-deficient rats with the highest concentration in the caudate nucleus, hypothalamus and cerebellum. Sub-cellular distribution studies showed the highest concentration to be in the crude mitochondrial fraction. The iron-deficient group had an approx. 60% decrease in brain iron stores. Measurement was also made of the monoamine metabolising enzymes (MAO) in iron-deficient rats. Despite large decreases in peripheral MAO activity no decrease in central MAO activity was observed in these rats. Nor was there any decrease in brain tryptophan hydroxylase or aldehyde dehydrogenase activity. In very severe iron-deficient (haemoglobin 4.5 ± 0.6 g/dl) rats, brain MAO activity still decreased only by 15.70% while heart MAO activity decreased by over 60%, while there was still no change in tryptophan hydroxylase activity. Iron deficient rats showed decreased behavioural responses following increased brain 5-hydroxytryptamine (5-HT) synthesis or after administration of the 5-HT agonist 5-methoxy N, N-dimethyltryptamine. They also showed decreased behavioural responses following administration of tranylcypromine plus l-DOPA, methamphetamine or apomorphine. No change in brain tryptophan or 5-HT synthesis was observed although endogenous 5-HT content was decreased. No changes were seen in brain dopamine or noradrenaline content, nor in the activity of dopamine-sensitive adenylate cyclase. Brain protein synthesis was also unaltered. Eight days after restoration of the iron plus diet the behavioural responses were normalised, but injection of ferrous gluconate (acutely) failed to restore the behaviour. Reasons for the altered post-synaptic monoamine behavioural responses being unlikely to be the result of anaemia are discussed and the relevance of decreased monoamine function in iron-deficiency is also discussed, particularly with regard to the high incidence of this nutritional disorder.