Effect of dimethyl fumarate on the changes in the medial prefrontal cortex structure and behavior in the poly(I:C)-induced maternal immune activation model of schizophrenia in the male mice.

ABSTRACT

BACKGROUND: The link between maternal immune activation (MIA) and the risk of developing schizophrenia (SCZ) later in life has been of major focus in recent years. This link could be bridged by activated inflammatory pathways and excessive cytokine release resulting in adverse effects on behavior, histology, and cytoarchitecture. The down-regulatory effects of immunomodulatory agents on the activated glial cells and their therapeutic effects on schizophrenic patients are consistent with this hypothesis. OBJECTIVE: We investigated whether treatment with the anti-inflammatory drug dimethyl fumarate (DMF) could rescue impacts of prenatal exposure to polyinosinicpolycytidylic acid [poly (IC)]. METHODS: Pregnant dams were administered poly(IC) at gestational day 9.5. Offspring born from these mothers were treated with DMF for fourteen consecutive days from postnatal day 80 and were assessed behaviorally before and after treatment. The brains were then stained with Cresyl Violet or Golgi-Cox. In addition to the estimation of stereological parameters, cytoarchitectural changes were also evaluated in the medial prefrontal cortex. RESULTS: MIA caused some abnormalities in behavior, as well as changes in the number of neurons and non-neurons. These alterations were also extended to pyramidal layer III neurons with a significant decrease in dendritic complexity and spine density which DMF treatment could prevent these changes. Furthermore, DMF treatment was also effective against abnormal exploratory and depression-related behavior, but not the changes in the number of cells. CONCLUSION: These findings support the idea of using anti-inflammatory agents as adjunctive therapy in patients with SCZ.