| First Author | Park SJ | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 8502 | PubMed ID | 25687169 |
| Mgi Jnum | J:274060 | Mgi Id | MGI:6218872 |
| Doi | 10.1038/srep08502 | Citation | Park SJ, et al. (2015) Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice. Sci Rep 5:8502 |
| abstractText | 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-3alpha/beta 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-3alpha/beta 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-3alpha/beta signaling. |
