https://scholars.lib.ntu.edu.tw/handle/123456789/43488
標題: | BEHAVIORAL PHENOTYPING OF V-AKT MURINE THYMOMA VIRAL ONCOGENE HOMOLOG 1-DEFICIENT MICE REVEALS A SEX-SPECIFIC PREPULSE INHIBITION DEFICIT IN FEMALES THAT CAN BE PARTIALLY ALLEVIATED BY GLYCOGEN SYNTHASE KINASE-3 INHIBITORS BUT NOT BY ANTIPSYCHOTICS | 作者: | Chen, Y.W. WEN-SUNG LAI |
公開日期: | 2011 | 起(迄)頁: | 178-189 | 來源出版物: | Neuroscience | 摘要: | Schizophrenia is a severe mental illness with a strong genetic predisposition. Accumulating evidence from human genetics and animal studies suggest v-akt murine thymoma viral oncogene homolog 1 (Akt1) might contribute to susceptibility for schizophrenia. In contrast to inconclusive findings in human genetic studies, a mutant mouse model is a simplified and alternative approach to determining the biological functions of AKT1 and its possible role in the pathogenesis of schizophrenia. In study 1, a comprehensive battery of behavioral tests was performed on both male and female mice. The results of behavioral phenotyping did not reveal significant differences between genotypes or sexes, except increased time of immobility in the tail suspension test and acoustic prepulse inhibition (PPI) deficits in Akt1-knockout females. On the basis of the observed PPI deficit, in study 2a, neuromorphological alterations were examined with morphometric analysis of green fluorescent protein (GFP)-labeled pyramidal neurons in the auditory cortex of female mice. The results indicated abnormalities in the architecture and complexity of the neurons of mutant females compared with those of the controls. In study 2b, potentially effective pharmacological treatments were explored to mitigate the observed PPI deficits in females. Antipsychotics (either raclopride (3 mg/kg) or clozapine (3 mg/kg)) did not alleviate observed PPI deficits in Akt1-knockout females but it was partially normalized by 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT, 5 mg/kg) and SB216763 (2.5 mg/kg). These findings imply the importance of AKT1 in some behavioral phenotypes and dendritic morphology in the auditory cortex of female mice, and they also suggest that subjects with Akt1 deficiency are insensitive to antipsychotic drugs, whereas glycogen synthase kinase-3 (GSK3) inhibitors could have therapeutic potential for the treatment of acoustic PPI deficits. ? 2011 IBRO. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/239541 | DOI: | 10.1016/j.neuroscience.2010.09.056 | SDG/關鍵字: | 2 (2,4 dichlorophenyl) 3 (1 methyl 3 indolyl)maleimide; 2 dipropylamino 8 hydroxytetralin; clozapine; glycogen synthase kinase 3 inhibitor; green fluorescent protein; neuroleptic agent; protein kinase B; raclopride; animal behavior; animal cell; animal experiment; animal model; animal tissue; article; auditory cortex; cell structure; controlled study; dendrite; dose response; drug mechanism; drug resistance; drug sensitivity; drug targeting; enzyme activity; enzyme deficiency; enzyme localization; experimental test; female; genotype; immobilization; knockout mouse; male; morphometrics; mouse; nonhuman; phenotype; prepulse inhibition; priority journal; pyramidal nerve cell; sex difference; signal transduction; tail suspension test; task performance; 8-Hydroxy-2-(di-n-propylamino)tetralin; Acoustic Stimulation; Animals; Antipsychotic Agents; Auditory Cortex; Clozapine; Dendrites; Fear; Female; Glycogen Synthase Kinase 3; Indoles; Male; Maleimides; Maze Learning; Mice; Mice, Knockout; Motor Activity; Phenotype; Proto-Oncogene Proteins c-akt; Pyramidal Cells; Raclopride; Sex Factors; Startle Reaction |
顯示於: | 心理學系 |
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