ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Regulation of copper transport crossing brain barrier systems by Cu-ATPases: effect of manganese exposure.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 57 citations in OpenAlex.
- Emerging role of copper in the pathophysiology of spinal cord injury.Neural regeneration research · 2026Article
- Zinc and Copper Metallic Instability: Investigating Altered Metal Functionality in both Human and Animal Studies.Biological trace element research · 2026Review
- Transcriptome-Based WGCNA Reveals Hub Genes Involved in Copper Resistance ofInternational journal of molecular sciences · 2026Article
- Choroid plexus modulates subventricular zone adult neurogenesis and olfaction through secretion of small extracellular vesicles.Fluids and barriers of the CNS · 2026Article
- The gut-liver-kidney-brain axis in Wilson disease: copper speciation-flux and barrier-mediated organ crosstalk.Frontiers in immunology · 2026Review
- Choroid Plexus Modulates Subventricular Zone Adult Neurogenesis and Olfaction Through Secretion of Small Extracellular Vesicles.Research square · 2025Article
- Preclinical Theranostic Profiling of [Molecules (Basel, Switzerland) · 2025Article
- Cellular mechanisms of copper neurotoxicity in human, differentiated neurons.Archives of toxicology · 2025Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Copper-coordination driven brain-targeting nanoassembly for efficient glioblastoma multiforme immunotherapy by cuproptosis-mediated tumor immune microenvironment reprogramming.Journal of nanobiotechnology · 2024Article
- Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice.Environmental health perspectives · 2024Article
- The Role of Copper Overload in Modulating Neuropsychiatric Symptoms.International journal of molecular sciences · 2024Review
- Transcriptomics-based investigation of manganese dioxide nanoparticle toxicity in rats' choroid plexus.Scientific reports · 2023Article
- High affinity of β-amyloid proteins to cerebral capillaries: implications in chronic lead exposure-induced neurotoxicity in rats.Fluids and barriers of the CNS · 2023Article
- Atp7b-dependent choroid plexus dysfunction causes transient copper deficit and metabolic changes in the developing mouse brain.PLoS genetics · 2023Article
- Copper Modulates Adult Neurogenesis in Brain Subventricular Zone.International journal of molecular sciences · 2022Article
- Ankylosing spondylitis complicated with andersson lesion in the lower cervical spine: A case report.World journal of clinical cases · 2022Article
- Age-dependent decline of copper clearance at the blood-cerebrospinal fluid barrier.Neurotoxicology · 2022Article
- Crossroads between membrane trafficking machinery and copper homeostasis in the nerve system.Open biology · 2021Review
- Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance.Biomolecules · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Regulation of cellular copper (Cu) homeostasis involves Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. The question as to how these Cu-ATPases in brain barrier systems transport Cu, i.e., toward brain parenchyma, cerebrospinal fluid (CSF), or blood, remained unanswered. This study was designed to characterize roles of Cu-ATPases in regulating Cu transport at the blood-brain barrier (BBB) and blood-CSF barrier (BCB) and to investigate how exposure to toxic manganese (Mn) altered the function of Cu-ATPases, thereby contributing to the etiology of Mn-induced parkinsonian disorder. Studies by quantitative real-time RT-PCR (qPCR), Western blot, and immunocytochemistry revealed that both Cu-ATPases expressed abundantly in BBB and BCB. Transport kinetic studies by in situ brain infusion and ventriculo-cisternal (VC) perfusion in Sprague Dawley rat suggested that the BBB was a major site for Cu entry into brain, whereas the BCB was a predominant route for Cu efflux from the CSF to blood. Confocal evidence showed that the presence of excess Cu or Mn in the choroid plexus cells led to ATP7A relocating toward the apical microvilli facing the CSF, but ATP7B toward the basolateral membrane facing blood. Mn exposure inhibited the production of both Cu-ATPases. Collectively, these data suggest that Cu is transported by the BBB from the blood to brain, which is mediated by ATP7A in brain capillary. By diffusion, Cu ions move from the interstitial fluid into the CSF, where they are taken up by the BCB. Within the choroidal epithelial cells, Cu ions are transported by ATP7B back to the blood. Mn exposure alters these processes, leading to Cu dyshomeostasis-associated neuronal injury.
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