Biogenic Monoamine Metabolism and Functional Activity in Iron‐Deficient Rats: Behavioural Correlates

Youdim, Moussa B. H.; Green, A. R.

doi:10.1002/9780470720325.ch10

Cited by 34 publications

(13 citation statements)

References 37 publications

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“…Thus, any changes in the activities of these enzymes may alter the brain level of these neurotransmitters at specific sites (hypothalamus, striatum, raphe nucleus, frontal cortex and hippocampus) in the brain and alter the physiology of their respective neurons as a consequence of over-or under-production of the neurotransmitters. Indeed we demonstrated that while NID in rats, as induced by feeding them a diet low in iron (5 ppm) results in the reduction of iron dependent enzymes (monoamine oxidase, phenylalanine hydroxylase, succinic dehydrogenase, cytochrome oxidase, to mention a few) in peripheral tissues, by contrast none of the brain enzymes containing iron, including tyrosine hydroxylase, tryptophan hydroxylase and monoamine oxidase) as a cofactor were changed (Youdim and Green, 1977;Youdim et al, 1989) (Table I). This was in spite of the fact that rat brain iron was reduced by 30-40% in adult (48 days old) in the striatum, hippocampus, cortex and raphe nucleus.…”

Section: Nid and Brain Ironmentioning

confidence: 93%

“…These investigators reported respectively that NID in children induced behavioral abnormalities that included a reduction of learning abilities (cognitive impairments), and that NID in rats fed an iron deficient diet results in the reduction of brain iron, albeit not as much as that in the liver. These reports together with the earlier studies of Spatz (Hallgren and Sourander, 1958;Pollitt et al, 1989) on the uneven distribution of iron in human brain prompted us to investigate the brain biochemical, pharmacological, physiological and behavioral effects of NID in rats as a model for the human condition (see Youdim and Green, 1977;Youdim et al, 1989). Our original hypothesis was based on the notion that the behavioral changes noted in iron deficient children by Webb and Oski (1973) were related to changes in the metabolism of CNS aminergic neurotransmitters, dopamine, serotonin and noradrenaline.…”

Section: Nid and Brain Ironmentioning

confidence: 94%

“…The unchanged activities of brain neurotransmitter enzymes in ID rats are complimented with unaltered brain (striatum, caudate nucleus and raphe nucleus) levels and turnover of dopamine, noradrenaline and serotonin (Youdim and Green, 1977;Youdim et al, 1989) (Table II). Nevertheless our animal behavioral studies with functional activities of neurotransmitters dopamine and serotonin indicated a highly significant degree of deficit, which for the first time complimented the "behavioral" deficits reported by Webb and Oski (Webb and Oski, 1973) in children with NID.…”

Section: Nid and Brain Ironmentioning

confidence: 96%

“…While rat (47 days old) liver iron and FER stores can be reduced relatively fast (within two weeks by 80-90%) brain iron is hardly changed until 3-5 weeks on the ID diet. Indeed newborn pups (10 days old) are more readily made ID than young (21 days old) animals (Dallman et al, 1975;Dallman and Spirito, 1977;Youdim and Green, 1977;BenShachar et al, 1986;Youdim et al, 1989).…”

Section: Nid and Brain Ironmentioning

confidence: 96%

“…Nevertheless our animal behavioral studies with functional activities of neurotransmitters dopamine and serotonin indicated a highly significant degree of deficit, which for the first time complimented the "behavioral" deficits reported by Webb and Oski (Webb and Oski, 1973) in children with NID. The neurochemical explanation for the behavioral deficits was not easily forthcoming and we suggested that brain ID may result in alteration in receptor number and function for any of these neurotransmitters (Youdim and Green, 1977). However, the abilities to measure various brain neurotransmitter receptor B max (receptor number) and K a , employing radioligands did not become available until 1976.…”

Section: Nid and Brain Ironmentioning

confidence: 97%

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Brain iron deficiency and excess; cognitive impairment and neurodegenration with involvement of striatum and hippocampus

Youdim

2008

neurotox res

114

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While iron deficiency is not perceived as a life threatening disorder, it is the most prevalent nutritional abnormality in the world, and a better understanding of modes and sites of action, can help devise better treatment programs for those who suffer from it. Nowhere is this more important than in infants and children that make up the bulk of iron deficiency in society. Although the effects of iron deficiency have been extensively studied in systemic organs, until very recently little attention was paid to its effects on brain function. The studies of Oski at Johns Hopkin Medical School in 1974, demonstrating the impairment of learning in young school children with iron deficiency, prompted us to study its relevance to brain biochemistry and function in an animal model of iron deficiency. Indeed, rats made iron deficient have lowered brain iron and impaired behaviours including learning. This can become irreversible especially in newborns, even after long-term iron supplementation. We have shown that in this condition it is the brain striatal dopaminergic-opiate system which becomes defective, resulting in alterations in circadian behaviours, cognitive impairment and neurochemical changes closely associated with them. More recently we have extended these studies and have established that cognitive impairment may be closely associated with neuroanatomical damage and zinc metabolism in the hippocampus due to iron deficiency, and which may result from abnormal cholinergic function. The hippocampus is the focus of many studies today, since this brain structure has high zinc concentration and is highly involved in many forms of cognitive deficits as a consequence of cholinergic deficiency and has achieved prominence because of dementia in ageing and Alzheimer's disease. Thus, it is now apparent that cognitive impairment may not be attributed to a single neurotransmitter, but rather, alterations and interactions of several systems in different brain regions. In animal models of iron deficiency it is apparent that dopaminergic interaction with the opiate system and cholinergic neurotransmission may be defective.

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Section: Nid and Brain Ironmentioning

confidence: 93%