Dopamine D(3) receptor deficiency sensitizes mice to iron deficiency-related deficits in motor learning

Klinker, Florian; Hasan, Kenan; Dowling, Pascal; Paulus, Walter; Liebetanz, David

doi:10.1016/j.bbr.2011.02.022

Cited by 5 publications

(2 citation statements)

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“…Yet despite the efficacy of the D3R compounds in treating RLS symptoms, there is no clinical evidence of A11 dysfunction in patients (Earley et al, 2009 ). However, a dysfunction of the DA system has been linked to altered iron homeostasis or iron-deficient diet (Dowling et al, 2011 ; Klinker et al, 2011 ; Dauvilliers and Winkelmann, 2013 ; Earley et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Meneely

Dinkins

Kassai

et al. 2018

Front. Behav. Neurosci.

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Restless Legs Syndrome (RLS) is often and successfully treated with dopamine receptor agonists that target the inhibitory D3 receptor subtype, however there is no clinical evidence of a D3 receptor dysfunction in RLS patients. In contrast, genome-wide association studies in RLS patients have established that a mutation of the MEIS1 gene is associated with an increased risk in developing RLS, but the effect of MEIS1 dysfunction on sensorimotor function remain unknown. Mouse models for a dysfunctional D3 receptor (D3KO) and Meis1 (Meis1KO) were developed independently, and each animal expresses some features associated with RLS in the clinic, but they have not been compared in their responsiveness to treatment options used in the clinic. We here confirm that D3KO and Meis1KO animals show increased locomotor activities, but that only D3KO show an increased sensory excitability to thermal stimuli. Next we compared the effects of dopaminergics and opioids in both animal models, and we assessed D1 and D3 dopamine receptor expression in the spinal cord, the gateway for sensorimotor processing. We found that Meis1KO share most of the tested behavioral properties with their wild type (WT) controls, including the modulation of the thermal pain withdrawal reflex by morphine, L-DOPA and D3 receptor (D3R) agonists and antagonists. However, Meis1KO and D3KO were behaviorally more similar to each other than to WT when tested with D1 receptor (D1R) agonists and antagonists. Subsequent Western blot analyses of D1R and D3R protein expression in the spinal cord revealed a significant increase in D1R but not D3R expression in Meis1KO and D3KO over WT controls. As the D3R is mostly present in the dorsal spinal cord where it has been shown to modulate sensory pathways, while activation of the D1Rs can activate motoneurons in the ventral spinal cord, we speculate that D3KO and Meis1KO represent two complementary animal models for RLS, in which the mechanisms of sensory (D3R-mediated) and motor (D1R-mediated) dysfunctions can be differentially explored.

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Section: Introductionmentioning

confidence: 99%

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Meneely

Dinkins

Kassai

et al. 2018

Front. Behav. Neurosci.

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“…anaemia and lowered body mass) (Weinberg et al, 1980;Youdim et al, 1989;Beard et al, 1993;Pollit, 1993). ID is a widespread form of malnutrition and is known to interfere with cognitive performance and development (Klinker et al, 2011). ID anaemia (IDA) or ID non-anaemia (IDNA) has been demonstrated to reduce iron content in animal brains.…”

Section: Introductionmentioning

confidence: 99%

Neurobehavioural analysis of developmental iron deficiency inOreochromis aureus × Oreochromis niloticus

Bai

Wang

Zhao

et al. 2014

Journal of Fish Biology

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The objective of this study was to examine the association between brain iron measurements of monoamine function and behavioural measurements of learning and memory. Male hybrid tilapias Oreochromis aureus × Oreochromis niloticus were fed either an iron-deficient (ID) diet or an iron-adequate (IA) diet for 8 weeks. The ID fishes showed significantly lower iron content in brain and decreasing learning and memory capacity. The fishes that showed increased learning and memory capacity had higher levels of iron and monoamine oxidase activity in brain. In addition, the results showed that learning and memory behaviours were related to monoamine (dopamine and noradrenaline) concentration in the brain. This suggests that iron can enhance learning and memory capacity in fishes and that the effect may have monoaminergic mediation in discrimination learning and memory tasks. The experimental data suggest that the properties and neural basis of learning and memory of teleosts are notably similar to those of land vertebrates.

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Combined D3 Receptor/Iron-Deficient Mouse Model

Klinker¹,

Liebetanz²

2015

Movement Disorders

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Dopamine D(3) receptor deficiency sensitizes mice to iron deficiency-related deficits in motor learning

Cited by 5 publications

References 20 publications

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Neurobehavioural analysis of developmental iron deficiency inOreochromis aureus × Oreochromis niloticus

Combined D3 Receptor/Iron-Deficient Mouse Model

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