A mouse model of schizophrenia induced by autoantibodies against SFT2D2

Schizophrenia (SCZ) is a highly heterogeneous, severe neuropsychiatric disorder of unknown etiopathology. Increasing data indicate an overlap between schizophrenia and pathological processes related to immunological dysregulation as well as inflammation, such as high levels of pro-inflammatory substances in patients' blood and cerebrospinal fluid and autoantibodies against synaptic and nerve cell membrane proteins. Autoantibodies against SFT2D2 have been reported in patients with SCZ. However, their roles in inflammation have not yet been established. We performed a continuous intracerebroventricular infusion of polyclonal rabbit anti-SFT2D2-IgG in male C57BL/6 mice. Behavioral tests were conducted after 2 weeks of treatment. Our results showed an increased density of microglia and activated astrocytes in the primary somatosensory cortex of the anti-SFT2D2-IgG-infused mice. Quantitative reverse transcription-polymerase chain reactions showed that the expression of pro-inflammatory genes was upregulated in the primary somatosensory cortex and hippocampus of the anti-SFT2D2-IgG-infused mice. Additionally, the mice exhibited defective sensorimotor gating, memory deficits, motor impairment, and anxiety-related behaviors without signs of depression. These findings indicate that anti-SFT2D2 autoantibodies can induce encephalitis, cause a series of behavioral changes associated with schizophrenia, and offer a model for testing novel therapies to improve treatment strategies for a subgroup of patients with SCZ.