Figure 12.

Schematic diagram showing the effect of prenatal exposure to VPA on the pathological changes in brains of young-adult male offspring. A single i.p. injection of VPA at 12.5 days of pregnancy-induced brain structure-specific defects in the expression of key pre- and postsynaptic proteins, consequently leading to pathological alterations in the structure of the synaptic endings (the hippocampus and cerebral cortex). In the hippocampus, the importance of oxidative stress and ROS generation in synaptic pathology is suggested. In the cerebral cortex, in addition to oxidative stress and ROS generation, neuroinflammation associated with microglia mobilization and M1 activation have also been proposed as potential triggers of a molecular cascade leading to synaptopathology. VPA induced long-lasting changes in microglia status in a brain structure-specific manner. In the cerebral cortex, both the pro-inflammatory M1 and the potentially beneficial recovery-promoting M2 phenotype were activated, while in the hippocampus, only M2 was stimulated.