Importin α1/KPNA1 is a member of the Importin α family widely present in the mammalian brain and has been characterized as a regulator of neuronal differentiation, synaptic functionality, and anxiety-like behavior. In humans, a de novo mutation of the KPNA1 (human Importin α5) gene has been linked with schizophrenia; however, the precise roles of KPNA1 in disorder-related behaviors are still unknown. Moreover, as recent studies have highlighted the importance of gene-environment interactions in the development of psychiatric disorders, we investigated the effects of Kpna1 deletion and social isolation stress, a paradigm that models social stress factors found in human patients, on psychiatric disorder-related behaviors in mice. Through assessment in a behavioral battery, we found that Kpna1 knockout resulted in the following behavioral phenotype: (1) decreased anxiety-like behavior in an elevated plus maze test, (2) short term memory deficits in novel object recognition test (3) impaired sensorimotor gating in a prepulse inhibition test. Importantly, exposure to social isolation stress resulted in additional behavioral abnormalities where isolated Kpna1 knockout mice exhibited: (1) impaired aversive learning and/or memory in the inhibitory avoidance test, as well as (2) increased depression-like behavior in the forced swim test. Furthermore, we investigated whether mice showed alterations in plasma levels of stress-associated signal molecules (corticosterone, cytokines, hormones, receptors), and found that Kpna1 knockout significantly altered levels of corticosterone and LIX (CXCL5). Moreover, significant decreases in the level of prolactin were found in all groups except for group-housed wild type mice. Our findings demonstrate that Kpna1 deletion can trigger widespread behavioral abnormalities associated with psychiatric disorders, some of which were further exacerbated by exposure to adolescent social isolation. The use of Kpna1 knockout mice as a model for psychiatric disorders may show promise for further investigation of gene-environment interactions involved in the pathogenesis of psychiatric disorders.
This study investigated the reparative and adaptive changes of periodontium following traumatic occlusion. The arrangement of actin filaments and proliferative activity of periodontium were carefully assessed. The left and right side maxillary second premolars of nine Japanese monkeys were used for the experiment, and the left and right side maxillary second molars were employed as control teeth . Trauma from occlusion was created by the method of Kitamura (1990) . After removing crowns of the maxillary and mandibular cuspids, the buccal cusps of the second premolars were intentionally elongated with casting onlays to induce bruxism force. The animals were sacrificed after 2, 4, and 8 weeks . One half of the sections were stained with hematoxylin-eosin, and the other half were observed by immunohistochemistry for actin and proliferative cell nuclear antigen (PCNA) . Tissue changes due to trauma from occlusion were divided into three stages: injury stage (until 2 weeks) , reparative stage (4 weeks) and adaptive (8 weeks) . In the injury stage, PCNA-positive cells were detected at the periphery of blood vessels of the bone defect. Both PCNA-positive cells and actin filaments were found at the periphery of blood vessels of the periodontium after 4 weeks, and were recognizable at the surfaces of the cementum and alveolar bone after 8 weeks. These results may suggest that the reparative changes were initiated by the cells around the remodelled perivascular region and later involvess cells adjacent to the cementum and alveolar bone . J.Jpn. Soc. Periodontol., 41: 1-15, 1999.
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