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ToxSci Advance Access originally published online on March 22, 2006
Toxicological Sciences 2006 91(2):532-539; doi:10.1093/toxsci/kfj172
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Imaging the Peripheral Benzodiazepine Receptor Response in Central Nervous System Demyelination and Remyelination

Ming-Kai Chen and Tomás R. Guilarte1

Molecular Neurotoxicology Laboratory, Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland 21205

Received December 19, 2005; accepted March 20, 2006

We used a rodent model of cuprizone-induced demyelination to examine the peripheral benzodiazepine receptor (PBR) response during remyelination. C57BL/6J mice were fed a 0.2% cuprizone-containing or control diet for 3 weeks and then removed to allow for remyelination. Quantitative autoradiography of 3H-(R)-PK11195 binding to PBR in the corpus callosum showed increased levels at 3 weeks of demyelination and gradually decreased as a function of remyelination. PBR levels were associated with the degree of remyelination and activation of microglia and astrocytes. However, the temporal pattern suggests that the PBR signal during the late stages of remyelination was primarily associated with astrocytes. We also used small-animal positron-emission tomography (PET) imaging to determine if this technique could be used to monitor PBR levels in the brain of living mice. The results indicate that 11C-(R)-PK11195 levels are significantly elevated in the mouse brain during cuprizone-induced demyelination and normalize at a time in which remyelination is complete. These findings support the notion that PBR is a sensitive marker for the visualization and quantification of brain injury and recovery. Further, the in vivo imaging of the PBR response is now possible in the living rodent brain.

Key Words: peripheral benzodiazepine receptor (PBR); (R)-PK11195; demyelination; remyelination; cuprizone; microglia; astrocyte; positron-emission tomography (PET).


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