| Summary: | 碩士 === 國立臺灣大學 === 解剖學暨細胞生物學研究所 === 101 === Schizophrenia affects approximately 1% of the population worldwide. Impaired mental functions, emotions and behaviors are characteristics of this disease; besides, cognitive processes including perception and judgment are also devastated in patients with schizophrenia. Multiple factors, including genetic defects, prenatal and postnatal environmental insults, are thought to be involved in the pathogenic process of the illness. In this study, we aimed to explore the singular and synergistic effects of factors of different origins that may interactively affect the behavioral performances related to schizophrenia in mice. We administered a viral mimic, polyriboinosinic- polyribocytidilic acid (Poly I:C, 20 mg/Kg, ip), to pregnant B6 mice at gestation day 9 to simulate prenatal immune challenge. After P30, male offspring were kept in group (group-rearing) or individually (isolation-rearing). After P60, phenotypes were characterized in various aspects. We first examined the emotion-related behaviors. Though there was no difference among four groups in elevated plus maze test, prenatal infection and long-term isolation produced synergistic effects on reducing immobility in the forced swimming test. We next evaluated the hippocampus-related cognitive functions using Morris water maze. Compared to the control group, impaired spatial memory was evident in mice treated with prenatal infection and social isolation simultaneously. Besides, all social isolated mice exhibited worse memory ability. Morphologically, the dendritic architecture of the granule cells in the dentate gyrus was examined. Reduced dendritic complexity and spine density were found in all experiment groups. Moreover, in Poly I:C offspring, more microglia were counted in hippocampus at P2 but not at P80, suggesting that the fetal immune system was transiently activated by prenatal infection. Finally, we assessed the density of GABAergic interneurons and oligodendrocytes by GAD67 and GST-π immunohistochemistry, respectively. There was no change found among all groups suggesting that prenatal infection and social isolation did not affect the number of GABAergic neurons and oligodendrocytes. Together, singular and synergistic effects of prenatal infection and social isolation on the structure and function of the dentate gyrus were noticed. The interplay of prenatal and postnatal environmental insults in relation to mental illness was demonstrated.
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