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Contact: Donna Krupa
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Office: (301) 634-7209
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dkrupa@the-aps.org
Exercise Protects Against Damage Causing Leakage in
the Blood Brain Barrier Following Meth Use in Mice
NEW ORLEANS—Regular exercise can prevent the
disruption of the blood brain barrier that normally occurs with a dose of
methamphetamine comparable to that used by heavy meth users.
A University of Kentucky study is the first to look at
the protective effects of exercise on the vascular effects of
methamphetamine, effects that have been found clinically to contribute to
serious, lasting, and sometimes fatal cardiovascular and neurological
problems. Results of the study, conducted in young male mice, were reported
April 22 at the Experimental Biology 2009 meeting in New Orleans. The
presentation was part of the scientific program of The American
Physiological Society (APS;
www.the-aps.org/press).
Principal investigator Dr. Michal Toborek says the
level of the protective effects of exercise on the integrity of the blood
brain barrier after the human equivalent of one gram of methamphetamine was
surprising even to the research team.
The results provide new understanding of the mechanisms
through which the brain reacts to methamphetamine, particularly those
related to oxidative stress. Results also suggest why exercise might help
delay the onset of neurodegenerative diseases such as Alzheimer’s and
Parkinson’s in which leakiness of the blood brain barrier is a
characteristic.
The researchers placed 25 young male mice – aged three
months, equivalent to the 20s in humans -- in cages where they had access to
exercise wheels. For five weeks, the animals took advantage of the wheels to
run continually. Another 25 young mice were housed in similar cages but
without access to wheels.
At the end of this “endurance exercise training”
period, all mice were injected with 10 mg. of methamphetamine over a 24-hour
period. All the mice displayed some of the same effects of meth as seen in
humans: they appeared agitated and increased their physical activity, and
their body temperature rose. But in terms of what was happening in the
capillaries of the brain, there was a marked difference between the mice who
had been exercising extensively for the previous five weeks and those who
had been sedentary.
In the sedentary group of mice, the small capillaries
in the brain experienced increased oxidative stress, causing the blood brain
barrier to become more permeable. Toxins and inflammatory cells previously
prevented from crossing the blood brain barrier then had access to the
brain. The exercise group showed no such changes.
Changes in the blood brain barrier, especially the role
of oxidative reactions, have been little studied in the past, says Dr.
Toborek; the University of Kentucky study is the first to observe that meth
administration produced an upregulation of NADPH oxidase, a major enzyme
that causes oxidative stress.
This is a significant finding, says Dr. Toborek,
because it delineates a mechanism for how meth causes oxidative stress. It
also was significant that the exercise mice were markedly protected from
such upregulation and consequently from the oxidative stress that weakened
the capillaries in the brains of the non-exercise mice.
Exercise by no means protects against all the harmful
effects of meth use, says Dr. Toborek, and the team now plans to study the
effects and mechanisms involved in chronic meth abuse. However, he says,
this study adds to the growing amount of data showing the positive and
protective health effects of consistent exercise.
A physician by training, Dr. Toborek is a professor in
the Department of Neurosurgery with joint appointments in molecular
biochemistry and nutrition. Co-authors on the study are postdoctoral fellows
Dr. Melissa Seelbach, Dr. Yean Jung Choi, and Dr. Lei Chen and research
associate Dr. Andras Ibolya, all in Neurosurgery; Dr. Bernhard Henning,
College of Agriculture; and Dr. Karyn Esser, physiology. The research was
supported by the National Institute of Mental Health, NIH and the University
of Kentucky Center for Muscle Biology.
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Physiology
is the study of how molecules, cells, tissues and organs function to create
health or disease. The American Physiological Society (APS;
www.The-APS.org/press) has been an integral part of this discovery
process since it was established in 1887.
NOTE TO EDITORS: The APS annual meeting is part
of the Experimental Biology 2009 (EB ’09) gathering and will be held April
18-22, 2009 at the New Orleans Convention Center. To schedule an interview
with a member of the research team, please contact Donna Krupa at
301.634.7209 (office), 703.967.2751 (cell) or
DKrupa@the-APS.org.
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