Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice

• DOI: 10.1038/srep08502
• Publication Date: 2015-02-17T10:06:48Z
• Authors: Se Jin Park; Jee Youn Lee; Sang Jeong Kim; Se-Young Choi; Tae Young Yune; Jong Hoon Ryu
• Keywords: Mice, Knockout; Behavior, Animal; Cell Death; Anxiety; Hyperkinesis; Article; Toll-Like Receptor 2; Cerebral Ventricles; 3. Good health; Disease Models, Animal; Glycogen Synthase Kinase 3; Mice; 03 medical and health sciences; 0302 clinical medicine; Schizophrenia; Animals; Cognition Disorders; Proto-Oncogene Proteins c-akt; Psychomotor Performance; Antipsychotic Agents; Signal Transduction

AbstractDysregulation 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 aTLR-2deficiency may contribute to the development and/or pathophysiology of schizophrenia-like behaviors via Akt-GSK-3α/β signaling.