Iron and iron management proteins in neurobiology

Connor, James R.; Menzies, S. L.; Burdo, Joseph; Boyer, Philip J.

doi:10.1016/s0887-8994(01)00303-4

Cited by 160 publications

(161 citation statements)

References 89 publications

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“…Though unexpected, this observation may indicate upregulation of other potential Mn transport mechanisms found in the striatum such as DMT-1 (Roth and Garrick, 2003;Burdo et al, 1999), a transporter with an expanding role in regulating Mn concentrations (Erikson et al, 2004), voltage-gated calcium channels (Yokel and Crossgrove, 2004) or even the transferrin receptor (Connor et al, 2001;Malecki et al, 1999). Additionally, since Mn concentrations were not decreased by drug treatment under normal conditions, this supports data from a previous study that DAT may only be involved in Mn transport during toxic conditions .…”

Section: Discussionmentioning

confidence: 97%

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

Anderson

Cooney

Erikson

2007

Environmental Toxicology and Pharmacology

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Manganese (Mn) is an essential nutrient, though exposure to high concentrations may result in neurotoxicity characterized by alterations in dopamine neurobiology. To date, it remains elusive how and why Mn targets dopaminergic neurons although recently the role of the dopamine transporter has been suggested. Our primary goal of this study was to examine the potential roles of the monoamine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET), in neuronal Mn transport. Using striatal synaptosomes, we found that only inhibition of DAT significantly decreased Mn accumulation. Furthermore, weanling rats chronically exposed to Mn, significantly accumulated Mn in several brain regions. However, rats receiving the specific DAT inhibitor GBR12909 (1 mg/kg bw, three times/week; four weeks) had significantly lower Mn levels only in the globus pallidus compared to saline-treated rats (p<0.05). Our data show that inhibition of DAT exclusively inhibits Mn accumulation in the globus pallidus during chronic exposure.

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Section: Discussionmentioning

confidence: 97%

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

Anderson

Cooney

Erikson

2007

Environmental Toxicology and Pharmacology

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“…Fig. 7, patients 1 and 3), a region identified as the zone of active inflammation with an influx of iron-rich macrophages in post-gadolinium images of acute plaques and as containing globular structures of non-heme iron in histological studies of older plaques (Connor et al, 2001;Haacke et al, 2005). Comparing the phase shift with gadolinium enhancement could potentially be used to differentiate past (chronic) from present (acute) inflammation and the quantity of deposited blood products in chronic plaques could indicate the level of past activity.…”

Section: Phase Images Of Patients With Multiple Sclerosismentioning

confidence: 99%

Development of a robust method for generating 7.0 T multichannel phase images of the brain with application to normal volunteers and patients with neurological diseases

et al. 2008

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The increased susceptibility effects and high signal-to-noise ratio at 7T enable imaging of the brain using the phase of the magnetic resonance signal. This study describes and evaluates a robust method for calculating phase images from gradient-recalled echo (GRE) scans. The GRE scans were acquired at 7T using an eight-channel receive coil at spatial resolutions up to 0.195×0.260×2.00mm. The entire 7T protocol took less than 10 minutes. Data was acquired from forty-seven subjects including clinical patients with multiple sclerosis (MS) or brain tumors. The phase images were post-processed using a fully automated phase unwrapping algorithm that combined the data from the different channels. The technique was used to create the first phase images of MS patients at any field strength and the first phase images of brain tumor patients above 1.5T. The clinical images showed novel contrast in MS plaques and depicted microhemorrhages and abnormal vasculature in brain tumors with unsurpassed resolution and contrast.

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“…Iron and its regulatory proteins play a critical role in development and are likely important in defining the selective vulnerability of the developing brain to traumatic injury. Iron is necessary for growth and cellular differentiation due to its role as a constituent of molecules generating mitochondrial energy, such as cytochrome c. 120 Iron regulation is partly governed by transferrin, a transport protein, and ferritin, a storage protein. 120 These two molecules bind iron when it is not a component of ironcontaining moieties such as hemoglobin, myoglobin, and cytochrome molecules.…”

Section: Iron Accumulation In the Injured Brainmentioning

confidence: 99%

“…Iron is necessary for growth and cellular differentiation due to its role as a constituent of molecules generating mitochondrial energy, such as cytochrome c. 120 Iron regulation is partly governed by transferrin, a transport protein, and ferritin, a storage protein. 120 These two molecules bind iron when it is not a component of ironcontaining moieties such as hemoglobin, myoglobin, and cytochrome molecules. Transferrin and ferritin are thus important in limiting the cytotoxic effects of iron.…”

Section: Iron Accumulation In the Injured Brainmentioning

confidence: 99%

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

Potts

Koh

Whetstone

et al. 2006

NeuroRX

139

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Summary: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality among children and both clinical and experimental data reveal that the immature brain is unique in its response and vulnerability to TBI compared to the adult brain. Current therapies for pediatric TBI focus on physiologic derangements and are based primarily on adult data. However, it is now evident that secondary biochemical perturbations play an important role in the pathobiology of pediatric TBI and may provide specific therapeutic targets for the treatment of the head-injured child. In this review, we discuss three specific components of the secondary pathogenesis of pediatric TBIinflammation, oxidative injury, and iron-induced damage -and potential therapeutic strategies associated with each. The inflammatory response in the immature brain is more robust than in the adult and characterized by greater disruption of the blood-brain barrier and elaboration of cytokines. The immature brain also has a muted response to oxidative stress compared to the adult due to inadequate expression of certain antioxidant molecules. In addition, the developing brain is less able to detoxify free iron after TBI-induced hemorrhage and cell death. These processes thus provide potential therapeutic targets that may be tailored to pediatric TBI, including anti-inflammatory agents such as minocycline, antioxidants such as glutathione peroxidase, and the iron chelator deferoxamine.

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Iron and iron management proteins in neurobiology

Cited by 160 publications

References 89 publications

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

Inhibition of DAT function attenuates manganese accumulation in the globus pallidus

Development of a robust method for generating 7.0 T multichannel phase images of the brain with application to normal volunteers and patients with neurological diseases

Traumatic injury to the immature brain: Inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets

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