Opening the blood-brain barrier to zinc

Blair‐West, J. R.; Denton, Derek A.; Gibson, A.; McKinley, MJ

doi:10.1016/0006-8993(90)90513-b

Cited by 22 publications

(7 citation statements)

References 21 publications

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“…One may wonder how dietary zinc might act so quickly on the central nervous system (CNS) and regulate a function as essential as sleep. It is well accepted that the blood–brain barrier (BBB) has a very low permeability for zinc and the concentration of this ion remains extremely stable in the CSF regardless of serum zinc concentration [ 73 ]. However, a higher time-resolution measurement in rats revealed a rapid exchange of zinc between blood and brain during the first 30 min following intravenous administration, and zinc was not stored in the CSF but in an undetermined compartment of the brain [ 74 , 75 ].…”

Section: Solving the Mystery Of Zinc-induced Sleepmentioning

confidence: 99%

Dietary Zinc Acts as a Sleep Modulator

Chérasse

Urade

2017

IJMS

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While zinc is known to be important for many biological processes in animals at a molecular and physiological level, new evidence indicates that it may also be involved in the regulation of sleep. Recent research has concluded that zinc serum concentration varies with the amount of sleep, while orally administered zinc increases the amount and the quality of sleep in mice and humans. In this review, we provide an exhaustive study of the literature connecting zinc and sleep, and try to evaluate which molecular mechanism is likely to be involved in this phenomenon. A better understanding should provide critical information not only about the way zinc is related to sleep but also about how sleep itself works and what its real function is.

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Section: Solving the Mystery Of Zinc-induced Sleepmentioning

confidence: 99%

Dietary Zinc Acts as a Sleep Modulator

Chérasse

Urade

2017

IJMS

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“…Two early studies found that Zn uptake into the rat brain across cerebral capillaries was about 20 nmol/day/brain, while that across the choroid plexus was less than 0.2 nmol/day/brain, as a consequence of the low influx rate across the BCB, the normal Zn level in CSF is 0.15 mM, only accounts for about 1% that of plasma. [65][66][67][68][69] These findings suggest that the major supply path for Zn is via the BBB, whereas the choroid plexus may involve in a slow supply for Zn to the brain. [70][71][72] ZnT2 acts to transport Zn molecules into intracellular vesicles for storage.…”

Section: Discussionmentioning

confidence: 95%

Upregulation of zinc transporter 2 in the blood–CSF barrier following lead exposure

Zeng

Zheng

et al. 2013

Exp Biol Med (Maywood)

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Zinc (Zn) is an essential element for normal brain function; an abnormal Zn homeostasis in brain and the cerebrospinal fluid (CSF) has been implied in the etiology of Alzheimer’s disease (AD). However, the mechanisms that regulate Zn transport in the blood–brain interface remain unknown. This study was designed to investigate Zn transport by the blood–CSF barrier (BCB) in the choroid plexus, with a particular focus on Zn transporter-2 (ZnT2), and to understand if lead (Pb) accumulation in the choroid plexus disturbed the Zn regulatory function in the BCB. Confocal microscopy, quantitative PCR and western blot demonstrated the presence of ZnT2 in the choroidal epithelia; ZnT2 was primarily in cytosol in freshly isolated plexus tissues but more toward the peripheral membrane in established choroidal Z310 cells. Exposure of rats to Pb (single ip injection of 50mg Pb acetate/kg) for 24 h increased ZnT2 fluorescent signals in plexus tissues by confocal imaging and protein expression by western blot. Similar results were obtained by in vitro experiments using Z310 cells. Further studies using cultured cells and a two-chamber Transwell device showed that Pb treatment significantly reduced the cellular Zn concentration and led to an increased transport of Zn across the BCB, the effect that may be due to the increased ZnT2 by Pb exposure. Taken together, these results indicate that ZnT2 is present in the BCB; Pb exposure increases the ZnT2 expression in choroidal epithelial cells by a yet unknown mechanism and as a result, more Zn ions may be deposited into the intracellular Zn pool, leading to a relative Zn deficiency state in the cytoplasm at the BCB.

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“…There is a concern that elevated concentrations of zinc in the brain contribute to the progression of Alzheimer's disease and other neuropathologies [3,12]. Zinc supplements are being consumed in amounts that exceed the recommended dietary allowance [37].…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular zinc in the brain has also been implicated in the development of cerebral amyloid angiopathy [10] and advanced Alzheimer's disease [11]. There are several potential mechanisms by which an impairment in brain zinc homeostasis might influence the progression of Alzheimer's disease and other neuropathologies [3,12].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal changes in zinc transport kinetics, metallothionein and zinc transporter expression in a blood–brain barrier model in response to a moderately excessive zinc environment

Bobilya

Gauthier

Karki

et al. 2008

The Journal of Nutritional Biochemistry

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A blood-brain barrier (BBB) model composed of porcine brain capillary endothelial cells (BCEC) was exposed to a moderately excessive zinc environment (50 micromol/L Zn) in cell culture, and longitudinal measurements were made of zinc transport kinetics, ZnT-1 (SLC30A1) expression and changes in the protein concentration of metallothionein (MT), ZnT-1, ZnT-2 (SLC30A2) and Zip1 (SLC39A1). Zinc release by cells of the BBB model significantly increased after 12-24 h of exposure, but decreased back to control levels after 48-96 h, as indicated by transport across the BBB from both the ablumenal (brain) and the lumenal (blood) directions. Expression of ZnT-1, the zinc export protein, increased by 169% within 12 h, but was no longer different from controls after 24 h. Likewise, ZnT-1 protein content increased transiently after 12 h of exposure, but returned to control levels by 24 h. Capacity for zinc uptake and retention increased from both the lumenal and the ablumenal directions within 12-24 h of exposure and remained elevated. MT and ZnT-2 were elevated within 12 h and remained elevated throughout the study. Zip1 was unchanged by the treatment. The BBB's response to a moderately high zinc environment was dynamic and involved multiple mechanisms. The initial response was to increase the cells' capacity to sequester zinc with additional MT and to increase zinc export with the ZnT-1 protein. But the longer-term strategy involved increasing ZnT-2 transporters, presumably to sequester zinc into intracellular vesicles as a mechanism to protect the brain and to maintain brain zinc homeostasis.

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Opening the blood-brain barrier to zinc

Cited by 22 publications

References 21 publications

Dietary Zinc Acts as a Sleep Modulator

Dietary Zinc Acts as a Sleep Modulator

Upregulation of zinc transporter 2 in the blood–CSF barrier following lead exposure

Longitudinal changes in zinc transport kinetics, metallothionein and zinc transporter expression in a blood–brain barrier model in response to a moderately excessive zinc environment

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