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Molecular Neurodegeneration

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Open Access 01-12-2011 | Research article

Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

Authors: P M Abdul Muneer, Saleena Alikunju, Adam M Szlachetka, L Charles Murrin, James Haorah

Published in: Molecular Neurodegeneration | Issue 1/2011

Abstract

Background

Methamphetamine (METH), an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial cell activation. Here we hypothesized that METH-induced interference of glucose uptake and transport at the endothelium can disrupt the energy requirement of the blood-brain barrier (BBB) function and integrity. We undertake this study because there is no report of METH effects on glucose uptake and transport across the blood-brain barrier (BBB) to date.

Results

In this study, we demonstrate that METH-induced disruption of glucose uptake by endothelium lead to BBB dysfunction. Our data indicate that a low concentration of METH (20 μM) increased the expression of glucose transporter protein-1 (GLUT1) in primary human brain endothelial cell (hBEC, main component of BBB) without affecting the glucose uptake. A high concentration of 200 μM of METH decreased both the glucose uptake and GLUT1 protein levels in hBEC culture. Transcription process appeared to regulate the changes in METH-induced GLUT1 expression. METH-induced decrease in GLUT1 protein level was associated with reduction in BBB tight junction protein occludin and zonula occludens-1. Functional assessment of the trans-endothelial electrical resistance of the cell monolayers and permeability of dye tracers in animal model validated the pharmacokinetics and molecular findings that inhibition of glucose uptake by GLUT1 inhibitor cytochalasin B (CB) aggravated the METH-induced disruption of the BBB integrity. Application of acetyl-L-carnitine suppressed the effects of METH on glucose uptake and BBB function.

Conclusion

Our findings suggest that impairment of GLUT1 at the brain endothelium by METH may contribute to energy-associated disruption of tight junction assembly and loss of BBB integrity.

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Title: Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction
Authors: P M Abdul Muneer
Saleena Alikunju
Adam M Szlachetka
L Charles Murrin
James Haorah
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2011
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-6-23

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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