The specific goal of this project is to determine the extent to which variations in brain iron concentration, that occur as a natural phenotypic variation, or as augmented phenotypes induced by dietary iron restriction, result in alterations of DA synthesis, release, re-uptake, and kinetics, and their associated impact upon motor reflex activity and circadian regulation of motor activity. The long-term plan of this project is to establish an animal model for RLS, but the immediate focus is to establish a biological model for exploring the relationship of iron to the dopaminergic system. In this project, we utilize two strains of recombinant inbred strains of mice to explore the potential mechanisms through which brain iron variances can alter the DA system, and associated behaviors.
The aims of the current project are:
Aim 1 : To determine the extent to which brain iron variances can effect DA metabolism during the active and inactive phases of the diurnal cycle.
Aim 2 : To assess the degree to which brain iron variance results in alterations in behaviors regulated by DA pathways.
Aim 3 : To determine the extent to which brain iron variance will alter the """"""""normal"""""""" DA response to chronic DA agonist treatment.
Aim 4 : To explore how chronic treatment with L-dopa will affect the behaviors explored in Aim 2.
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| Allen, Richard P; Donelson, Nathan C; Jones, Byron C et al. (2017) Animal models of RLS phenotypes. Sleep Med 31:23-28 |
| Skeba, Patrick; Hiranniramol, Kasidet; Earley, Christopher J et al. (2016) Inter-movement interval as a primary stable measure of periodic limb movements of sleep. Sleep Med 17:138-43 |
| Allen, Richard P (2015) Restless Leg Syndrome/Willis-Ekbom Disease Pathophysiology. Sleep Med Clin 10:207-14, xi |
| Unger, Erica L; Bianco, Laura E; Jones, Byron C et al. (2014) Low brain iron effects and reversibility on striatal dopamine dynamics. Exp Neurol 261:462-8 |
| Unger, E L; Jones, B C; Bianco, L E et al. (2014) Diurnal variations in brain iron concentrations in BXD RI mice. Neuroscience 263:54-9 |
| Unger, E L; Earley, C J; Thomsen, L L et al. (2013) Effects of IV iron isomaltoside-1000 treatment on regional brain iron status in an iron-deficient animal. Neuroscience 246:179-85 |
| Allen, Richard P; Barker, Peter B; Horská, Alena et al. (2013) Thalamic glutamate/glutamine in restless legs syndrome: increased and related to disturbed sleep. Neurology 80:2028-34 |
| Jellen, L C; Lu, L; Wang, X et al. (2013) Iron deficiency alters expression of dopamine-related genes in the ventral midbrain in mice. Neuroscience 252:13-23 |
| Earley, Christopher J; Kuwabara, Hiroto; Wong, Dean F et al. (2013) Increased synaptic dopamine in the putamen in restless legs syndrome. Sleep 36:51-7 |
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