PS149. Interleukin-18-deficient mice develop dysfunction of hippocampus resulting in depression-like behavior

s | 51 gyrus (DG) fail to mature (Yamasaki et al., Mol. Brain, 2008; Hagihara et al. Cell Reports, in press), in several genetic mouse models that display behavioral abnormalities related to psychiatric disorders. Additionally, chronic administration of fluoxetine, selective serotonin reuptake inhibitor, which is used to treat depression, induces “dematuration” of DG neurons: mature DG neurons go back to pseudo-immature state (Kobayashi et al., PNAS, 2010). However, whether there is any relationship between stress and maturation of DG remains to be understood. Here, we examined the effects of repeated stress on maturation of DG neurons in C57BL/6J mice and BALB/c mice, which are known to be more susceptible to stress and more anxious than C57BL/6J mice. Animals were subjected to repeated restraint stress for 3 or 6 weeks. The gene and protein expressions of maturation markers of DG neurons were analyzed by real-time PCR and immunohistochemical methods, and anxiety-like and depression-like behaviors were assessed. Repeated stress downregulated maturation markers (desmoplakin, tryptophan 2, 3-dioxygenase, and calbindin) and upregulated an immature marker (BDNF) in BALB/c mice. No changes of such markers were detected in C57BL/6J mice. Repeated stress also led to decreased protein expressions of calbindin and glucocorticoid receptor in the DG of BALB/c mice. Additionally, repeated stress induced hyperlocomotor activity and increased depression-like behaviors in BALB/c mice. These results suggest that repeated restraint stress alters maturation state of the DG neurons in BALB/c mice, which may underlie some of the stress-induced behavioral changes. PS149 Interleukin-18-deficient mice develop dysfunction of hippocampus resulting in depression-like behavior Kyosuke Yamanishi1,6, Nobutaka Doe4,5, Kaoru Ikubo1, Miho Sumida5, Sachi Kuwahara-Otani2, Seishi Maeda2, Yuko Watanabe6, Momoko Yoshida6, Wen Li3, Tetsu Hayakawa3, Haruki Okamura3, Hiromichi Yamanishi6 and Hisato Matsunaga1 1Department of Neuropsychiatry, 2Department of Anatomy and Cell Biology, 3Laboratory of Tumor Immunology and Cell Therapy, and 4Laboratory of Neurogenesis and CNS Repair, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya, 663–8501, 5Department of Psychology, Hyogo University of Health Sciences, 1-3-6, Minatojima, Chuo-ku, Kobe, Hyogo 650–8530, 6Hirakata General Hospital for Developmental Disorders, 2-1-1 Tsudahigashi, Hirakata, Osaka 573-