Voluntary exercise protects against methamphetamine-induced oxidative stress in brain microvasculature and disruption of the blood–brain barrier

Molecular Neurodegeneration

Karyn A Esser⁴  Minseon Park³  Lei Chen⁵  Ibolya E András³  Cetewayo S Rashid²  Melissa J Seelbach¹  Michal Toborek³ 

[1] Department of Neurosurgery, University of Kentucky, Lexington, KY, USA;Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY, USA;Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Gautier Bldg, Room 528, 1011 NW 15th Street, 33136, Miami, USA;Department of Physiology, University of Kentucky, Lexington, KY, USA;Department of Neuroscience, Mount Sinai School of Medicine, New York, USA

关键词: Tight junctions;    Oxidative stress;    Blood-brain;    Exercise;    Drug abuse;    Methamphetamine;   

Others  :  862285
DOI  :  10.1186/1750-1326-8-22

 received in 2013-05-06, accepted in 2013-06-14,  发布年份 2013

【 摘 要 】

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 lab™ 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.

【 授权许可】

   
2013 Toborek et al.; licensee BioMed Central Ltd.

【 图 表 】

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