Nutritional iron and dopamine binding sites in the rat brain

Ashkenazi, Ruth; Ben‐Shachar, Dorit; Youdim, Moussa B. H.

doi:10.1016/0091-3057(82)90509-3

Cited by 130 publications

(54 citation statements)

References 32 publications

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“…Iron is also related with monoamine oxidase, which is critically related with degradation of dopamine. Iron is colocalized with dopaminergic neurons in the brain [8] and D2 and D4 receptor and dopamine transporter densities decrease with decreased brain iron levels [9,10]. All these results suggest that iron metabolism may have important role in ADHD pathophysiology.…”

Section: Introductionmentioning

confidence: 89%

“…Consistent with this previous studies [11,19], we found that lower ferritin levels were associated with higher problem scores. It has been found that iron is closely related to dopamine metabolism being a coenzyme of tyrosine hydroxylase, and that D2 and D4 receptor and dopamine transporter densities decrease with decreased brain iron levels [8][9][10]. It can be speculated that iron deficiency may cause further alterations in brain dopaminergic system, which seems to be already impaired in ADHD subjects [20].…”

Section: Discussionmentioning

confidence: 99%

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Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity

Öner¹,

Oner

2007

Child Psychiatry Hum Dev

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Our aim was to investigate the relation between behavioral symptoms and hematological variables which are related with iron deficiency and anemia, ferritin, hemoglobin, mean corpuscular volume (MCV), and reticulosite distribution width (RDW) in children and adolescents with pure Attention Deficit Hyperactivity Disorder (ADHD) or ADHD comorbid with other psychiatric disorders. The sample consisted of 151 subjects with ADHD, 45 of these subjects had other comorbid conditions. Conners Parent (CPRS) and Teacher Rating Scales (CTRS) were obtained. Comorbid ADHD subjects had lower mean hemoglogin and MCV. In the ADHD group in general, CPRS and CTRS Total scores were significantly negatively correlated with ferritin level. When only pure ADHD subjects were taken into account, the correlations did not reach statistical signifance. Overall, these results suggested that lower ferritin level was associated with higher behavioral problems reported by both parents and teachers. Presence of comorbid conditions might increase the effect of lower iron stores on behavioral measures.

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Section: Introductionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity

Öner¹,

Oner

2007

Child Psychiatry Hum Dev

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“…It has been well known that iron deficiency is one of the leading causes of symp tomatic RLS (Allen 2004). It has been suggested that iron is closely related to dopamine metabolism being a coenzyme of tyrosine hydroxylase, and that D2 and D4 receptor and dopamine transporter densities decrease with decreased brain iron levels (Ashkenazi et al 1982;Ericson et al 1997). In patients with RLS, reduced brain iron concentration may be due to dysfunctional iron transportation (Mizuno et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Association between Low Serum Ferritin and Restless Legs Syndrome in Patients with Attention Deficit Hyperactivity Disorder

Öner¹,

Dirik²,

Taner

et al. 2007

Tohoku J. Exp. Med.

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Attention defi cit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by pervasive inattention and/or hyperactivity-impulsivity. It has been suggested that ADHD symptoms are associated with restless legs syndrome (RLS), which is a neurological condition that is defi ned by an irresistible urge to move the legs. Increasing evidence suggests iron deficiency may underlie common pathophysiological mechanisms in subjects with ADHD and with RLS. To further defi ne the relationship between iron defi ciency and RLS in children and adolescents with ADHD, we evaluated 87 ADHD subjects: 79 boys and 8 girls with age 9.3 ± 2.5 years (6-16 years). Various psychopathologies and the severity of the ADHD symptoms and serum ferritin levels were assessed. Diagnosis of RLS was made according to the International RLS Group criteria. The patients were evaluated for the iron defi ciency (ferritin < 12 ng/ml). RLS was found in 29 (33.3%) of the 87 ADHD subjects. Parentand teacher-rated behavioral and emotional problems and the severity of ADHD symptoms were not signifi cantly different between ADHD subjects with RLS and those without RLS (n = 58). The rate of iron defi ciency was signifi cantly higher in ADHD subjects with RLS (n = 6, 20.7%) when compared with ADHD subjects without RLS (n = 1, 1.7%, p = 0.005). Our results showed that depleted iron stores might increase the risk of having RLS in ADHD subjects. Iron defi ciency, which is associated with both ADHD and RLS, seems to be an important modifying factor in the relationship between these two conditions. restless legs syndrome; attention defi cit hyperactivity disorder; iron defi ciency; ferritin; dopamine

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“…Iron deficiency influences the dopaminergic system on different levels. D2R and dopamine transporter (DAT) are downregulated in ID rats (Ashkenazi et al, 1982;Erikson et al, 2000). A decrease of inhibitory D2R activation leads to a preponderance of excitatory dopamine D 1 receptor (D1R) activation, which is associated with increased locomotor activity in rats (Shieh and Walters, 1996;Heijtz et al, 2002).…”

Section: D3r؊/؊ and Iron Deficiency Alter Circadian Motor Activitymentioning

confidence: 99%

Dopamine D₃Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice

Dowling¹,

Klinker²,

Stadelmann³

et al. 2011

J. Neurosci.

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Restless legs syndrome (RLS) is a common neurological disorder whose exact pathophysiological mechanism remains unclear despite the successful use of dopaminergic treatment and recent discovery of predisposing genetic factors. As iron deficiency has been associated with RLS for some patients and there is evidence for decreased spinal dopamine D 3 -receptor (D3R) signaling in RLS, we aimed at establishing whether D3R activity and iron deficiency share common pathways within the pathophysiology of RLS sensory and motor symptoms.Using a combined mouse model of iron deficiency and dopamine D 3 -receptor deficiency (D3RϪ/Ϫ), circadian motor symptoms were evaluated by continuous recording of spontaneous wheel running activity. Testing the acute and persistent pain responses with the hot-plate test and formalin test, respectively, assessed sensory symptoms.A 15 week iron-deficient (ID) diet alone increased acute and persistent pain responses as compared to control diet. As compared to C57BL/6 (WT), homozygous D3RϪ/Ϫ mice already exhibited elevated responses to acute and persistent pain stimuli, where the latter was further elevated by concurrent iron deficiency. ID changed the circadian activity pattern toward an increased running wheel usage before the resting period, which resembled the RLS symptom of restlessness before sleep. Interestingly, D3RϪ/Ϫ shifted this effect of iron deficiency to a time point 3-4 h earlier.The results confirm the ability of iron deficiency and D3RϪ/Ϫ to evoke sensory and motor symptoms in mice resembling those observed in RLS patients. Furthermore this study suggests an increase of ID-related sensory symptoms and modification of ID-related motor symptoms by D3RϪ/Ϫ.

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Nutritional iron and dopamine binding sites in the rat brain

Cited by 130 publications

References 32 publications

Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity

Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity

Association between Low Serum Ferritin and Restless Legs Syndrome in Patients with Attention Deficit Hyperactivity Disorder

Dopamine D₃Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice

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Nutritional iron and dopamine binding sites in the rat brain

Cited by 130 publications

References 32 publications

Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity

Relationship of Ferritin to Symptom Ratings Children with Attention Deficit Hyperactivity Disorder: Effect of Comorbidity

Association between Low Serum Ferritin and Restless Legs Syndrome in Patients with Attention Deficit Hyperactivity Disorder

Dopamine D3Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice

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Dopamine D₃Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice