期刊
BRAIN RESEARCH REVIEWS
卷 48, 期 2, 页码 207-210出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainresrev.2004.12.010
关键词
peripheral benzodiazepine receptor; activated microglia; neurodegenerative disease
Within the diseased brain, glial cells and in particular, microglia, express a multimeric protein complex termed peripheral benzodiazepine binding sites (PBBS) or peripheral benzodiazepine receptor (PBR). The expression of the PBBS is dependent on the functional state of the cell and in glial cells is triggered by a wide range of activating stimuli. In the healthy brain, the PBBS are nearly absent with the notable exception of the choroid plexus, ependymal layer, perivascular cells, central canal, possibly certain nuclei in the brainstem and layers in the cerebellum where a constitutive presence of the PBBS is found. Likewise, areas that due to the absence of the blood-brain barrier contain more active glial cells, such as the pituitary gland, or the area postrema at floor of the 4th ventricle show a degree of constitutive expression. The tight correlation of the parenchymal de novo expression of the PBBS with the presence of activated glial cells, that in turn are usually only found in tissue affected by progressive disease, establishes the PBBS as a generic marker for the detection and measurement of active disease processes in the brain. Specific radioligands of the PBBS for use in positron emission tomography (PET) may thus provide a sensitive in vivo index of neuropathological activity. Whilst prototype ligands for the PBBS are available, future research needs to focus on the development of new ligands with improved pharmacodynamic properties and the ability to discriminate between the different, still insufficiently understood functional states of the peripheral benzodiazepine receptor complex. (c) 2004 Elsevier B.V. All rights reserved.
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