title: Effects of translocator protein (18 kDa) ligands on microglial activation and neuronal death in the quinolinic-acid-injected rat striatum.
abstract: There is evidence that excitotoxicity and prolonged microglial activation are involved in neuronal death in neurodegenerative disorders. Activated microglia express various molecules, including the translocator protein 18 kDa (TSPO; formerly known as the peripheral benzodiazepine receptor) on the outer mitochondrial membrane. The TSPO is a novel target for neuroprotective treatments which aim to reduce microglial activation. The effect of PK 11195 and three other TSPO ligands on the level of microglial activation and neuronal survival was evaluated in a quinolinic acid (QUIN) rat model of excitotoxic neurodegeneration. All three ligands were neuroprotective at a level comparable to PK 11195. All of the ligands decreased microglial activation following the injection of QUIN but had no effect on astrogliosis. Interestingly, we also observed neuroprotective effects from the vehicle, dimethyl sulfoxide (DMSO).
authors.affiliation: Department of Pharmacology, Bosch Institute and School of Medical Sciences, University of Sydney, NSW 2006, Australia.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Leaver
authors.forename: Aaron
authors.initials: A
authors.lastname: Reynolds
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bodard
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008845:Microinjections; D017072:Neostriatum / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D014677:Pharmaceutical Vehicles; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D007546:Isoquinolines; D018696:Neuroprotective Agents; D014677:Pharmaceutical Vehicles; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D017378:Quinolinic Acid; C037850:PK 11195; D004121:Dimethyl Sulfoxide