title: Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice.
abstract: Dysregulation of the immune system contributes to the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we demonstrated that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms. Psychotic symptoms such as hyperlocomotion, anxiolytic-like behaviors, prepulse inhibition deficits, social withdrawal, and cognitive impairments were observed in TLR-2 knock-out (KO) mice. Ventricle enlargement, a hallmark of schizophrenia, was also observed in TLR-2 KO mouse brains. Levels of p-Akt and p-GSK-3α/β were markedly higher in the brain of TLR-2 KO than wild-type (WT) mice. Antipsychotic drugs such as haloperidol or clozapine reversed behavioral and biochemical alterations in TLR-2 KO mice. Furthermore, p-Akt and p-GSK-3α/β were decreased by treatment with a TLR-2 ligand, lipoteichoic acid, in WT mice. Thus, our data suggest that the dysregulation of the innate immune system by a TLR-2 deficiency may contribute to the development and/or pathophysiology of schizophrenia-like behaviors via Akt-GSK-3α/β signaling.
authors: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Korea.
authors: Se Jin
authors: SJ
authors: Park
authors: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors: Jee Youn
authors: JY
authors: Lee
authors: Department of Physiology, Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799, Korea.
authors: Sang Jeong
authors: SJ
authors: Kim
authors: Department of Physiology and Dental Research Institute, Seoul National University School of Dentistry, Seoul 110-749, Korea.
authors: Se-Young
authors: SY
authors: Choi
authors: 1] Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Korea [2] Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors: Tae Young
authors: TY
authors: Yune
authors: 1] Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Korea [2] Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea.
authors: Jong Hoon
authors: JH
authors: Ryu
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal; D016923:Cell Death / Q000235:genetics; D002552:Cerebral Ventricles / Q000473:pathology; D003072:Cognition Disorders / Q000235:genetics; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006948:Hyperkinesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011597:Psychomotor Performance; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D051195:Toll-Like Receptor 2; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3