Translocator protein 18 kDa is involved in the regulation of reactive gliosis.
Translocator protein (18 kDa) (TSPO), previously known as peripheral-type benzodiazepine receptor, is a critical component of the mitochondrial permeability transition pore. Brain inflammation results in the induction of the expression of TSPO in glial cells and some TSPO ligands decrease reactive gliosis after brain injury. However, since some TSPO ligands are neuroprotective, their effects on reactive gliosis may be the consequence of a reduced neurodegeneration. To assess whether TSPO ligands can modulate reactive gliosis in absence of neuronal death, we have tested their effects on the inflammatory response induced in the hippocampus of male rats by the intracerebroventricular infusion of lipopolysaccharide (LPS). LPS treatment did not induce neuronal death, assessed by Fluoro jade-B staining, but increased the number of cells immunoreactive for vimentin and MHC-II, used as markers of reactive astrocytes and reactive microglia, respectively. Furthermore, LPS produced an increase in the number of proliferating microglia. The TSPO ligand PK11195 reduced the number of MHC-II immunoreactive cells and the proliferation of microglia in LPS treated rats. In contrast, another TSPO ligand, Ro5-4864, did not significantly affect the response of microglia to LPS. Neither PK11195 nor Ro5-4864 affected the LPS-mediated increase in the number of vimentin-immunoreactive astrocytes at the time point studied, although PK11195 reduced vimentin immunoreactivity. These findings identify TSPO as a potential target for controlling neural inflammation, showing that the TSPO ligand PK11195 may reduce microglia activation by a mechanism that is independent of the regulation of neuronal survival.
Instituto Cajal, C.S.I.C., Madrid, Spain.
Sergio
S
Veiga
Paloma
P
Carrero
Olga
O
Pernia
Iñigo
I
Azcoitia
Luis Miguel
LM
Garcia-Segura
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001570:Benzodiazepinones / Q000494:pharmacology; D015415:Biomarkers; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D005452:Fluoresceins; D005911:Gliosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000378:metabolism; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008070:Lipopolysaccharides; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009930:Organic Chemicals; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D014746:Vimentin / Q000032:analysis / Q000378:metabolism
D000970:Antineoplastic Agents; D001570:Benzodiazepinones; D015415:Biomarkers; D005452:Fluoresceins; D000949:Histocompatibility Antigens Class II; D007546:Isoquinolines; D008024:Ligands; D008070:Lipopolysaccharides; D009930:Organic Chemicals; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C499229:TSPO protein, human; D014746:Vimentin; C435731:fluoro jade; C028513:4'-chlorodiazepam; C037850:PK 11195