From the Ferritin Lady: File #2

[Guest guest]

Biological mechanisms of the effect of iron deficiency on brain biochemistry

and behavior

Author: Youdim MB; Ben-Shachar D; Yehuda S

Address: Department of Pharmacology, Faculty of Medicine, Technion Medical

School, Haifa, Israel.

Source: Am J Clin Nutr, 1989 Sep, 50:3 Suppl, 607-15; discussion 615-7

Abstract: An animal model of nutritional iron deficiency (ID) is described

that demonstrates a reduction of brain nonheme iron. The most prominent

feature of ID is the significant and selective diminution of central dopamine

neurotransmission resulting from the decreased number of dopamine D2

receptors in the caudate nucleus, nucleus accumbens, pituitary, and in all

probability the frontal cortex. The consequences of diminished dopaminergic

neurotransmission is a modification of dopamine-dependent behaviors and

biochemical reactions, the most important of which is the reduction in

learning processes.

The role of iron in maintaining the homeostasis of normally

functioning dopamine neurons and their involvement in cognitive processes

cannot be excluded. An interference with iron metabolism at an early age can

result in irreversible damage to developing dopamine neurons, with

consequences that may manifest themselves in adult life.

Modulation of dopamine receptor in the striatum by iron: behavioral and

biochemical correlates

Author:Youdim MB; Ashkenazi R; Ben-Shachar D; Yehuda S

Source: Adv Neurol, 1984, 40:, 159-70

Abstract: The present study has shown that in the rat brain iron is unevenly

distributed and may be associated with the dopaminergic neuron. The function

of the large amounts of iron in certain brain areas, such as the pallidum,

caudate nucleus, substantia nigra, nucleus accumbens, and olfactory

tubercule, is not known. But it is obvious that by reduction of brain iron,

as in the case of nutritional iron deficiency, certain dopamine-mediated

behavioral phenomena and biochemical reactions are altered. These changes

have been attributed to the selective reduction in dopamine D2 receptors and

function in brain areas rich in dopamine neurons and iron. If iron is

especially important to dopaminergic modulatory systems in the brain, its

deficit might explain the increasing number of reports on behavioral

disturbances, EEG, and event-related potentials (ERPs) associated with

nutritional iron deficiency in children.

Minimal brain damage induced by early iron deficiency:

modified dopaminergic neurotransmission

Author: Youdim MB; Ben-Shachar D

Source: Isr J Med Sci, 1987 Jan-Feb, 23:1-2, 19-25

Abstract: The reports that iron-deficiency anemia in human subjects induces

behavioral changes was investigated in rats made nutritionally

iron-deficient. The most prominent features of these animals were: the

unchanged metabolism of the neurotransmitters noradrenaline, dopamine and

serotonin, profound reduction of brain nonheme iron, the selective diminution

of dopamine D2 receptor number (measured by Bmax), modification of

dopamine-dependent behaviors and reduction of learning processes. The

induction of these changes and their recovery with iron supplementation are

age- and time-dependent phenomena.

In newborn rats, however, the consequences of iron deficiency are

irreversible, even after long-term iron supplementation. The results point to

the profound effect iron metabolism can have on the long-term development and

function of dopaminergic neurotransmission. These findings may not be totally

unexpected, since iron distribution in the brain is highly localized in

dopaminergic-peptidergic regions, such as the globus pallidus, substantia

nigra, red nucleus, thalamus, caudate nucleus and nucleus accumbens. In some

regions its concentration is higher than that found in the liver, the site of

iron metabolism.

Effect of iron chelators on dopamine D2 receptors

Author: Ben-Shachar D; Finberg JP; Youdim MB

Source: J Neurochem, 1985 Oct, 45:4, 999-1005

Abstract: Nutritional iron deficiency induced in rats causes a selective

reduction of [3H]spiperone binding in caudate nucleus. This effect can be

reversed by iron supplementation in vivo. The possibility that iron may be

involved in the dopamine D2 receptor was investigated by examining the effect

of various iron and noniron chelators on the binding of [3H]spiperone in rat

caudate nucleus. Iron chelators 1,10-phenanthroline,

2,4,6-tripyridyl-s-triazine, alpha, alpha'-dipyridyl, and desferrioxamine

mesylate inhibited the binding of [3H]spiperone.

IRON DEFICIENCY AND THE BRAIN

Author: Parks YA; Wharton BA

Address: Community Health and Mental Handicap Services, Canterbury, UK.

Source: Acta Paediatr Scand Suppl, 1989, 361:, 71-7

Abstract: There is increasing evidence both from 'association' and

'intervention' studies that iron deficiency has an adverse effect on brain

function in animals and children. The severity and duration of iron

deficiency are important in determining the effect on development. Iron

replacement therapy has immediate (within 14 days) and long-term (over 3

months) beneficial effects on behaviour and psychomotor development. The

mechanisms for this probably involve a number of biochemical pathways in

which iron is essential. These include mitochondrial enzymes and various

neurotransmitters. Cytochrome C is reduced by iron deficiency but brain

tissue is relatively spared until the deficiency is severe. Levels of

neurotransmitters such as noradrenaline, serotonin and dopamine are all

altered during iron deficiency and this may explain some of the behavioural

and developmental changes that occur.