It was proposed by maternal immune activation (MIA) theory of schizophrenia that MIA stimulates microglia and enhances oxidative stress, which in turn diminishes neural functioning (6,37,38). Indeed, both post-mortem studies (39–42) and positron emission tomography (PET) study on recent-onset schizophrenia patients (43) has implicated the involvement of microglia in the pathophysiology of schizophrenia. Interestingly, involvement of microglial cells seems to be negligible in our NMDAR hypofunction mouse model. Neither proliferation of microglial cells (by anti-Iba1 staining, Figure S5C, D in Supplement 1), or microglial activation (by anti-CD68 staining, Figure S5E in Supplement 1), was observed in the cortex of Ppp1r2-cre/fGluN1 KO animals. Lack of microglial activation/proliferation in our mouse model may be due to the reason that the manipulation is targeted downstream of MIA in the developmental process of schizophrenia pathogenesis.
