Abstract
BACKGROUND: There is no effective therapeutic intervention developed targeting cerebrovascular toxicity of drugs of abuse, including methamphetamine (METH). We hypothesize that exercise protects against METH-induced disruption of the blood--brain barrier (BBB) by enhancing the antioxidant capacity of cerebral microvessels and modulating caveolae-associated signaling. Mice were subjected to voluntary wheel running for 5 weeks resembling the voluntary pattern of human exercise, followed by injection with METH (10 mg/kg). The frequency, duration, and intensity of each running session were monitored for each mouse via a direct data link to a computer and the running data are analyzed by Clock labTM Analysis software. Controls included mice sedentary that did not have access to running wheels and/or injections with saline.
RESULTS: METH induced oxidative stress in brain microvessels, resulting in up regulation of caveolae-associated NAD(P)H oxidase subunits, and phosphorylation of mitochondrial protein 66Shc. Treatment with METH disrupted also the expression and colocalization of tight junction proteins. Importantly, exercise markedly attenuated these effects and protected against METH-induced disruption of the BBB integrity.
CONCLUSIONS: The obtained results indicate that exercise is an important modifiable behavioral factor that can protect against METH-induced cerebrovascular toxicity. These findings may provide new strategies in preventing the toxicity of drug of abuse.
Document Type
Article
Publication Date
6-24-2013
Digital Object Identifier (DOI)
http://dx.doi.org/10.1186/1750-1326-8-22
Repository Citation
Toborek, Michal; Seelbach, Melissa J.; Rashid, Cetewayo S.; András, Ibolya E.; Chen, Lei; Park, Minseon; and Esser, Karyn A., "Voluntary exercise protects against methamphetamine-induced oxidative stress in brain microvasculature and disruption of the blood--brain barrier" (2013). Physiology Faculty Publications. 16.
https://uknowledge.uky.edu/physiology_facpub/16
Notes/Citation Information
Published in Molecular Neurodegeneration, v. 8, 22.
© 2013 Toborek et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.