Methamphetamine is not Toxic but Disrupts the Cell Cycle of Blood–Brain Barrier Endothelial Cells

Methamphetamine is not Toxic but Disrupts the Cell Cycle of Blood–Brain Barrier Endothelial Cells The cytotoxic effects of methamphetamine (MA) are well established to be caused via induced oxidative stress which in turn compromises the core function of the blood–brain barrier (BBB) by reducing its ability to regulate the homeostatic environment of the brain. While most studies were conducted over a period of 24–48 h, this study investigated the mechanisms by which chronic exposure of MA adversely affect the endothelial cells of BBB over an extended period of 96 h. MA induced significant depression of cell numbers at 96 h. This result was supported by flow cytometric data on the cell cycle which showed that brain endothelial cells (bEnd5) at 96 h were significantly suppressed in the S-phase of the cell cycle. In contrast, at 24–72 h control cell numbers for G1, S and G2-M phases were similar to MA-exposed cells. MA (0–1,000 µM) did not, however, statistically affect the viability and cytotoxicity of the bEnd5 cells, and the profile of ATP production and DNA synthesis (BrdU) across 96 h did not provide a rationale for the suppression of cell division. Our study reports for the first time that chronic exposure to MA results in long-term disruption of the cell cycle phases which eventuates in the attenuation of brain capillary endothelial cell growth after 96 h, compounding and contributing to the already well-known adverse short-term permeability effects of MA exposure on the BBB. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurotoxicity Research Springer Journals

Methamphetamine is not Toxic but Disrupts the Cell Cycle of Blood–Brain Barrier Endothelial Cells

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Publisher
Springer Journals
Copyright
Copyright © 2015 by Springer Science+Business Media New York
Subject
Biomedicine; Neurosciences; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology; Cell Biology
ISSN
1029-8428
eISSN
1476-3524
D.O.I.
10.1007/s12640-015-9520-5
Publisher site
See Article on Publisher Site

Abstract

The cytotoxic effects of methamphetamine (MA) are well established to be caused via induced oxidative stress which in turn compromises the core function of the blood–brain barrier (BBB) by reducing its ability to regulate the homeostatic environment of the brain. While most studies were conducted over a period of 24–48 h, this study investigated the mechanisms by which chronic exposure of MA adversely affect the endothelial cells of BBB over an extended period of 96 h. MA induced significant depression of cell numbers at 96 h. This result was supported by flow cytometric data on the cell cycle which showed that brain endothelial cells (bEnd5) at 96 h were significantly suppressed in the S-phase of the cell cycle. In contrast, at 24–72 h control cell numbers for G1, S and G2-M phases were similar to MA-exposed cells. MA (0–1,000 µM) did not, however, statistically affect the viability and cytotoxicity of the bEnd5 cells, and the profile of ATP production and DNA synthesis (BrdU) across 96 h did not provide a rationale for the suppression of cell division. Our study reports for the first time that chronic exposure to MA results in long-term disruption of the cell cycle phases which eventuates in the attenuation of brain capillary endothelial cell growth after 96 h, compounding and contributing to the already well-known adverse short-term permeability effects of MA exposure on the BBB.

Journal

Neurotoxicity ResearchSpringer Journals

Published: Feb 11, 2015

References

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