Tianeptine Affects the Improvement of Behavioral Defects, such as Schizophrenia, Caused by Maternal Immune Activation in the Mice Offspring.

Abstract

Simultaneously with studies on animal models of fetal-induced maternal immune activation, related studies documented behavior, neurophysiological, and/or neurochemical disorders observed in some neuropsychiatric disorders, including autism and schizophrenia. To investigate whether treatment tianeptine might ameliorate maternal immune activation (MIA)-induced behavioral deficits in the offspring. The pregnant mice were injected through tail vein injection at a concentration of 5 mg/kg of polyriboinosinic-polyribocytidilic acid (polyI:C) and/or used saline as a vehicle. The injection was performed on the 9th day of pregnancy. Each group of MIA offspring was subjected to vehicle, clozapine, or tianeptine treatment. In prepulse inhibition (PPI) test, oral treatment with tianeptine ameliorated MIA-induced sensorimotor gating deficit. Most behavioral parameters of social interaction test (SIT), forced swimming test (FST), and open field test (OFT) were significantly changed in the MIA offspring. Tianeptine treatment significantly recovered behavioral changes observed in the SIT, OFT, and FST. In order to confirm expression level of neurodevelopmental proteins, immunohistochemical image analysis and Western blot were performed, and the medial prefrontal cortex (mPFC) was targeted. As a result, it was confirmed that the neurodevelopmental proteins were decreased, which was recovered after administration of tianeptine to MIA offspring. Tianeptine might be useful for treating psychiatric disorders with neurodevelopmental issues.