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

Schizophrenia is a mental disorder often characterized by abnormal social behavior and failure to recognize what is real. Dysregulation of the immune system appears to play an important role in the pathogenesis of schizophrenia. Here, we show that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms.

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Firstly, we generated TLR KO mice and found only TLR-2 KO mice, but not TLR-3 or TLR-4 KO mice, showed abnormal and aggressive behaviors in a preliminary experiment. Deeply, TLR-2 KO mice show significant deficits in social behaviors, including impaired social recognition, reduced social interaction, and aggressive behavior.

Next, MRI data also showed that the volume of ventricles including the lateral, third, and fourth were significantly larger in TLR-2 KO mice than WT mice.  By Western blot analysis, we found that the levels of p-Akt and p-GSK-3a/b were markedly higher in the brain of TLR-2 KO than wild-type (WT) mice.

Finally, p-Akt and p-GSK-3a/b were decreased by treatment with a TLR-2 ligand, lipoteichoic acid, in WT mice.

In a word, behavioral alterations in TLR-2 KO mice were relevant to the symptoms of schizophrenia and marked dysregulation of Akt-GSK-3 signaling were also observed in the brain of TLR-2 KO mice, this study suggests that an alteration of TLR-2 functions in the CNS may contribute to schizophrenia etiology.