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Cellular and Subcellular Localization of Peripheral Benzodiazepine Receptors After Trimethyltin Neurotoxicity
Author(s) -
Kuhlmann Anthony C.,
Guilarte Tomás R.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741694.x
Subject(s) - microglia , glial fibrillary acidic protein , astrocyte , gliosis , astrocytosis , neurotoxicity , neuroglia , griffonia simplicifolia , hippocampal formation , immunohistochemistry , pathology , receptor , biology , chemistry , inflammation , neuroscience , central nervous system , medicine , immunology , toxicity , biochemistry
The peripheral benzodiazepine receptor (PBR) is currentlyused as a marker of inflammation and gliosis following brain injury. Previousreports suggest that elevated PBR levels in injured brain tissue are specificto activated microglia and infiltrating macrophages. We have producedhippocampal lesions using the neurotoxicant trimethyltin (TMT) to examine thecellular and subcellular nature of the PBR response. Degenerating,argyrophilic pyramidal neurons were observed in the hippocampus at 2 and 14days after TMT exposure. Reactive microglia were also evident at both timeswith a maximal response observed at 14 days, subsiding by 6 weeks.Astrocytosis was observed at 14 days and 6 weeks, but not 2 days, after TMTadministration, suggesting that the onset of the astroglia response isdelayed, but more persistent, compared with microgliosis. Morphologicalevidence from [ 3 H]PK11195 microautoradiography and PBRimmunohistochemistry indicates that both astrocytes and microglia are capableof expressing high levels of PBR after injury. This was confirmed by doublelabeling of either Griffonia simplicifolia isolectin B 4 , a microglial‐specific marker, or glial fibrillary acidic protein, an astrocyte‐specific protein with PBR fluorescence immunohistochemistry. These results demonstrate that PBR expression is increased after brain injury in both activated microglia and astrocytes. Our findings also provide the first evidence for in situ nuclear localization of PBR in glial cells.