Anxiogenic-Like Behavioral Phenotype of Mice Deficient in Phosphodiesterase 4B (PDE4B)
Anxiogenic-Like Behavioral Phenotype of Mice Deficient in Phosphodiesterase 4B (PDE4B)
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DOI：
10.1038/sj.npp.1301537
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发表时间：
2008-06
影响因子：
7.6
通讯作者：
Han-Ting Zhang;Ying Huang;Anbrin Masood;Lisa R Stolinski;Yunfeng Li;Lei Zhang;D. Dlaboga;S. Jin-S.-Ji
中科院分区：
文献类型：
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作者：
Han-Ting Zhang;Ying Huang;Anbrin Masood;Lisa R Stolinski;Yunfeng Li;Lei Zhang;D. Dlaboga;S. Jin-S.-Ji
磷酸二酯酶-4（PDE 4）是一种催化环腺苷酸水解的酶，在控制环腺苷酸细胞内浓度方面起着关键作用，与抑郁和焦虑样行为有关。然而，四个PDE 4亚家族（PDE 4A、PDE 4 B、PDE 4C和PDE 4D）的功能仍然在很大程度上未知。在对抗焦虑药、抗抑郁药、记忆增强剂或镇痛药敏感的动物试验中，我们检查了PDE 4 B缺陷小鼠（PDE 4 B −/−）的行为表型。免疫印迹分析显示，PDE 4 B −/−小鼠的大脑皮层和杏仁核中PDE 4 B表达缺失。PDE 4 B表达的减少伴随着PDE 4 B-/-小鼠大脑区域PDE 4活性的降低。与PDE 4 B +/+同窝小鼠相比，PDE 4 B −/−小鼠表现出焦虑样行为，表现为在孔板试验中头部下沉和头部下沉时间减少，在明-暗转换试验中转换和亮侧时间减少，以及在旷场试验中初始探索和直立减少。与致焦虑样行为一致，PDE 4 B −/−小鼠显示血浆皮质酮水平升高。此外，这些小鼠还表现出海马齿状回神经元细胞增殖的适度增加。在强迫游泳试验中，PDE 4 B −/−小鼠表现出不动性降低;然而，这并不支持尾部悬挂试验的结果。PDE 4 B −/−小鼠在记忆、运动活动或伤害性反应方面没有表现出变化。综上所述，这些结果表明，PDE 4 B亚家族参与了导致行为焦虑样效应的信号通路。
Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated in depression-and anxiety-like behaviors. However, the functions of the four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, and PDE4D) remain largely unknown. In animal tests sensitive to anxiolytics, antidepressants, memory enhancers, or analgesics, we examined the behavioral phenotype of mice deficient in PDE4B (PDE4B−/−). Immunoblot analysis revealed loss of PDE4B expression in the cerebral cortex and amygdala of PDE4B−/− mice. The reduction of PDE4B expression was accompanied by decreases in PDE4 activity in the brain regions of PDE4B−/− mice. Compared to PDE4B+/+ littermates, PDE4B−/− mice displayed anxiogenic-like behavior, as evidenced by decreased head-dips and time spent in head-dipping in the holeboard test, reduced transitions and time on the light side in the light–dark transition test, and decreased initial exploration and rears in the open-field test. Consistent with anxiogenic-like behavior, PDE4B−/− mice displayed increased levels of plasma corticosterone. In addition, these mice also showed a modest increase in the proliferation of neuronal cells in the hippocampal dentate gyrus. In the forced-swim test, PDE4B−/− mice exhibited decreased immobility; however, this was not supported by the results from the tail-suspension test. PDE4B−/− mice did not display changes in memory, locomotor activity, or nociceptive responses. Taken together, these results suggest that the PDE4B subfamily is involved in signaling pathways that contribute to anxiogenic-like effects on behavior.