Electroconvulsive seizures increase the expression of MAP kinase phosphatases in limbic regions of rat brain
Electroconvulsive seizures increase the expression of MAP kinase phosphatases in limbic regions of rat brain
复制标题
DOI：
10.1038/sj.npp.1300588
复制
发表时间：
2005-02-01
影响因子：
7.6
通讯作者：
Duman, RS
中科院分区：
文献类型：
--
作者：
Kodama, M;Russell, DS;Duman, RS
丝裂原活化蛋白(MAP)激酶级联调节多种细胞活动，包括细胞生长、增殖和凋亡，并被报道在抗抑郁治疗中发挥作用。有许多不同类别的蛋白磷酸酶可以影响MAP激酶级联反应。其中，MAP激酶磷酸酶(MKP)家族在激活的MAP激酶的去磷酸化过程中起着关键作用。在本研究中，我们分析了MKP1、MKP2和MKP3亚型在电惊厥发作(ECS)后大鼠脑内的表达，被认为是治疗抑郁症最有效的方法。原位杂交分析表明，ECS对MKP亚型的表达具有差异性调控作用。急性ECS后，海马齿状回颗粒细胞层、CA1和CA3锥体细胞层等主要细胞层的mkp1mRNA表达显著增加。相反，MKP2主要在齿状回表达，MKP3在CA1和CA3细胞层优先表达。在前额叶皮质，所有三种MKP亚型都被急性ECS上调。慢性ECS导致每一种MKP亚型的诱导模式相似，表明对重复ECS的反应很少或没有脱敏。MKP表达的诱导对MAP激酶级联反应起负反馈控制作用。上调MKP的表达可抑制ECS的作用，提示阻断MKPs可增强抗抑郁治疗的作用。
The mitogen-activated protein (MAP) kinase cascades regulate a variety of cellular activities, including cell growth, proliferation, and apoptosis, and are reported to play a role in the actions of antidepressant treatment. There are a number of different classes of protein phosphatases that could influence the MAP kinase cascade. One of these, the MAP kinase phosphatase (MKP) family, is known to play a key role in dephosphorylation of activated MAP kinase. In the present study, we analyzed the expression of the MKP1, MKP2, and MKP3 isoforms in rat brain after electroconvulsive seizure (ECS), considered the most effective treatment for depression. In situ hybridization analysis demonstrates that ECS differentially regulates the expression of the MKP isoforms. Expression of MKP1 mRNA is robustly increased by acute ECS in the major cell layers of the hippocampus, including the dentate gyrus granule cell layer and the CA1 and CA3 pyramidal cell layers. In contrast, MKP2 is induced mainly in the dentate gyrus and MKP3 is preferentially increased in the CA1 and CA3 cell layers. In the prefrontal cortex, all three MKP isoforms are upregulated by acute ECS administration. Chronic ECS resulted in a similar pattern of induction for each of the MKP subtypes, demonstrating that there is little or no desensitization of the response to repeated ECS. The induction of MKP expression serves as negative feedback control for the MAP kinase cascades. Upregulation of MKP expression could dampen the actions of ECS, indicating that blockade of the MKPs could enhance the actions of antidepressant treatment.