title: Chronic phencyclidine induces inflammatory responses and activates GSK3β in mice.
abstract: Use of phencyclidine (PCP) in rodents can mimic some aspects of schizophrenia. However, the underlying mechanism is still unclear. Growing evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. In this study, we focused on inflammatory responses as target of PCP for inducing schizophrenia-like symptoms. 3-month-old C57BL/6J mice received daily injections of PCP (20 mg/kg, i.p.) or saline for one week. PCP-injected mice produced schizophrenia-like behaviours including impaired spatial short-term memory assessed by the Y-maze task and sensorimotor gating deficits in a prepulse inhibition task. Simultaneously, chronic PCP administration induced astrocyte and microglial activation in both the cortex and hippocampus. Additionally, the proinflammatory cytokine interleukin-1β was significantly up-regulated in PCP administrated mice. Furthermore, PCP treatment decreased ratio of the phospho-Ser9 epitope of glycogen synthase kinase-3β (GSK3β) over total GSK3β, which is indicative of increased GSK3β activity. These data demonstrate that chronic PCP in mouse produces inflammatory responses and GSK3β activation.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 0T6, Canada.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhu
authors.forename: Hongxing
authors.initials: H
authors.lastname: Wang
authors.forename: Ruoyang
authors.initials: R
authors.lastname: Shi
authors.forename: Ruiguo
authors.initials: R
authors.lastname: Zhang
authors.forename: Junhui
authors.initials: J
authors.lastname: Wang
authors.forename: Lynda
authors.initials: L
authors.lastname: Kong
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Sun
authors.forename: Jue
authors.initials: J
authors.lastname: He
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Wang
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007249:Inflammation / Q000139:chemically induced*; D051379:Mice; D010622:Phencyclidine / Q000633:toxicity*
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D010622:Phencyclidine