Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats
Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats
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DOI：
10.1016/j.pnpbp.2012.11.015
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发表时间：
2013-06-03
影响因子：
5.6
通讯作者：
Lambas-Senas, Laura
中科院分区：
文献类型：
--
作者：
Abrial, Erika;Etievant, Adeline;Lambas-Senas, Laura
双相情感障碍的病理生理学和治疗的神经生物学机制仍然未知。近年来，蛋白激酶 C (PKC) 已成为躁狂症的潜在关键参与者。为了进一步研究该信号系统在情绪调节中的作用，我们研究了 PKC 调节剂在模拟双相情感障碍多个方面的行为测试和成年大鼠海马细胞增殖中的作用。我们的结果表明，单次注射 PKC 抑制剂他莫昔芬（80 mg/kg，腹腔注射）和白屈菜红碱（3 mg/kg，皮下注射）可减弱安非他明引起的过度运动并减少冒险行为，支持 PKC 阻断在急性躁狂中的功效。此外，长期暴露于他莫昔芬（10毫克/公斤/天，腹腔注射，持续14天）或白屈菜红碱（0.3毫克/公斤/天，皮下注射，持续14天）在强迫游泳测试中引起抑郁样行为，并导致海马齿状回细胞增殖减少。最后，我们发现，与 PKC 抑制剂相反，PKC 激活剂佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 可以增强冒险行为并诱导抗抑郁样作用。总而言之，这些发现支持 PKC 参与调节双相情感障碍的相反方面，并强调 PKC 在这种疾病中的重要作用。 (c) 2012 Elsevier Inc. 保留所有权利。
The neurobiological mechanisms underlying the pathophysiology and therapeutics of bipolar disorder are still unknown. In recent years, protein kinase C (PKC) has emerged as a potential key player in mania. To further investigate the role of this signaling system in mood regulation, we examined the effects of PKC modulators in behavioral tests modeling several facets of bipolar disorder and in adult hippocampal cell proliferation in rats. Our results showed that a single injection of the PKC inhibitors tamoxifen (80 mg/kg, i.p.) and chelerythrine (3 mg/kg, s.c.) attenuated amphetamine-induced hyperlocomotion and decreased risk-taking behavior, supporting the efficacy of PKC blockade in acute mania. Moreover, chronic exposure to tamoxifen (10 mg/kg/day, i.p., for 14 days) or chelerythrine (0.3 mg/kg/day, s.c., for 14 days) caused depressive-like behavior in the forced swim test, and resulted in a reduction of cell proliferation in the dentate gyrus of the hippocampus. Finally, we showed that, contrary to the PKC inhibitors, the PKC activator phorbol 12-myristate 13-acetate (PMA) enhanced risk-taking behavior and induced an antidepressant-like effect. Taken together, these findings support the involvement of PKC in regulating opposite facets of bipolar disorder, and emphasize a major role for PKC in this disease. (c) 2012 Elsevier Inc. All rights reserved.