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Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature.

Lei Chen¹, Robert A Yokel, Bernhard Hennig

¹Molecular Neuroscience and Vascular Biology Laboratory, Department of Neurosurgery, University of Kentucky Medical Center, 593 Wethington Bldg., 900 S Limestone, Lexington, KY 40536, USA.

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Summary

Nano-alumina exposure harms human brain cells and disrupts the blood-brain barrier in rats. Mitochondrial dysfunction appears to be the key mechanism behind this nanoparticle toxicity.

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Area of Science:

Environmental Science
Toxicology
Neuroscience

Background:

Manufactured aluminum oxide nanoparticles (nano-alumina) are increasingly prevalent in the environment.
Concerns are rising regarding the potential human health risks associated with nano-alumina exposure.

Purpose of the Study:

To investigate the hypothesis that nano-alumina can compromise the blood-brain barrier (BBB) and induce endothelial toxicity.
To explore the cellular mechanisms underlying nano-alumina-induced toxicity.

Main Methods:

Human brain microvascular endothelial cells (HBMEC) were exposed to nano-alumina to assess viability, mitochondrial potential, oxidative stress, and tight junction protein expression.
Rats were infused with nano-alumina, and brain tissue was analyzed for the expression and integrity of tight junction proteins (claudin-5, occludin).

Main Results:

Nano-alumina exposure significantly reduced HBMEC viability, altered mitochondrial membrane potential, and increased cellular oxidation.
Exposure to nano-alumina decreased the expression of tight junction proteins in HBMEC, an effect mitigated by glutathione.
In vivo, nano-alumina treatment led to fragmentation and disruption of claudin-5 and occludin in rat brains.
Mitochondrial dysfunction was identified as a potential underlying mechanism for nano-alumina toxicity.

Conclusions:

Nano-alumina can negatively impact cerebral vasculature integrity.
The disruption of mitochondrial function is implicated as a primary mechanism in nano-alumina toxicity, affecting the blood-brain barrier.