Molecular mechanism of distorted iron regulation in the blood–CSF barrier and regional blood–brain barrier following in vivo subchronic manganese exposure
| Autor: | G. Jane Li, Michael P. Waalkes, Byung-Sun Choi, Wei Zheng, Jie Liu, Xueqian Wang |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Pathology medicine.medical_specialty Time Factors Iron Transferrin receptor Toxicology Blood–brain barrier Article Rats Sprague-Dawley Cerebrospinal fluid In vivo Internal medicine Receptors Transferrin Parenchyma medicine Animals RNA Messenger Cerebrospinal Fluid Brain Chemistry Manganese Dose-Response Relationship Drug biology Reverse Transcriptase Polymerase Chain Reaction Chemistry Spectrophotometry Atomic General Neuroscience Brain Blotting Northern Rats Ferritin Dose–response relationship medicine.anatomical_structure Endocrinology Gene Expression Regulation Blood-Brain Barrier biology.protein Choroid plexus |
| Zdroj: | NeuroToxicology. 27:737-744 |
| ISSN: | 0161-813X |
| DOI: | 10.1016/j.neuro.2006.02.003 |
| Popis: | Previous studies in this laboratory indicated that manganese (Mn) exposure in vitro increases the expression of transferrin receptor (TfR) by enhancing the binding of iron regulatory proteins (IRPs) to iron responsive element-containing RNA. The current study further tested the hypothesis that in vivo exposure to Mn increased TfR expression at both blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier (BCB), which contributes to altered iron (Fe) homeostasis in the CSF. Groups of rats (10-11 each) received oral gavages at doses of 5 mg Mn/kg or 15 mg Mn/kg as MnCl(2) once daily for 30 days. Blood, CSF, and choroid plexus were collected and brain capillary fractions were separated from the regional parenchyma. Metal analyses showed that oral Mn exposure decreased concentrations of Fe in serum (-66%) but increased Fe in the CSF (+167%). Gel shift assay showed that Mn caused a dose-dependent increase of binding of IRP1 to iron responsive element-containing RNA in BCB in the choroid plexus (+70%), in regional BBB of capillaries of striatum (+39%), hippocampus (+56%), frontal cortex (+49%), and in brain parenchyma of striatum (+67%), hippocampus (+39%) and cerebellum (+28%). Real-time RT-PCR demonstrated that Mn exposure significantly increased the expression of TfR mRNA in choroid plexus and striatum with concomitant reduction in the expression of ferritin (Ft) mRNA. Collectively, these data indicate that in vivo Mn exposure results in Fe redistribution in body fluids through regulating the expression of TfR and ferritin at BCB and selected regional BBB. The disrupted Fe transport by brain barriers may underlie the distorted Fe homeostasis in the CSF. |
| Databáze: | OpenAIRE |
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