Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus.

Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus.
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DOI:
10.1017/s1461145704004304
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发表时间:
2004-09
期刊:
The international journal of neuropsychopharmacology
影响因子:
--
通讯作者:
T. Suenaga;S. Morinobu;K. Kawano;T. Sawada;S. Yamawaki
T. Suenaga;S. Morinobu;K. Kawano;T. Sawada;S. Yamawaki
中科院分区:
其他
文献类型:
--
作者:
T. Suenaga;S. Morinobu;K. Kawano;T. Sawada;S. Yamawaki

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钙/钙调素依赖性蛋白激酶(CaMK)II的磷酸化,由细胞内Ca 2+浓度的增加诱导,参与脑功能的改变,如记忆形成。在本研究中,我们研究了各种固定应激范式对大鼠海马中CaMKII磷酸化(磷酸化CaMKII)和CaMKII水平的影响。进行免疫印迹和免疫组织化学分析以检查CaMK II和磷酸化CaMK II的水平。采用实时定量聚合酶链反应(PCR)技术分析N-甲基-D-天冬氨酸(NMDA)和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体亚型的mRNA水平。45分钟或更长时间的急性(单次)和重复(4天)应激暴露显着增加了磷酸化CaMKII水平,但不影响CaMKII水平,但慢性(14天)应激暴露则不显着增加磷酸化CaMKII水平。预处理NBQX,选择性AMPA受体拮抗剂,显着防止这种压力诱导的增加。相比之下,两种NMDA受体拮抗剂LY 235959和MK-801在急性应激期间对磷酸化CaMK II水平没有抑制作用。无论是急性还是慢性应激都没有改变NMDA和AMPA受体的mRNA水平。这些结果表明,固定应激促进CaMKII的磷酸化。AMPA受体激活引起的细胞内Ca ~(2+)浓度的增加可能在应激诱导的大鼠海马磷酸化CaMK Ⅱ中起作用。
The phosphorylation of calcium/calmodulin-dependent protein kinase (CaMK) II, induced by an increase in the intracellular Ca2+ concentration, is involved in the alteration of brain functions such as memory formation. In the present study, we examined the influence of various immobilization stress paradigms on the phosphorylation of CaMKII (phospho-CaMKII) and CaMKII levels in the rat hippocampus. Immunoblot and immunohistochemical analyses were performed to examine the levels of CaMKII and phospho-CaMKII. Real-time quantitative polymerase chain reaction (PCR) was performed to analyse the mRNA levels of N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtypes. Acute (single) and repeated (4 d), but not chronic (14 d), stress exposure of 45 min or longer duration significantly increased phospho-CaMKII levels without affecting the levels of CaMKII. Pre-treatment with NBQX, a selective AMPA receptor antagonist, significantly prevented this stress-induced increase. In contrast, two NMDA receptor antagonists, LY235959 and MK-801, showed no inhibitory effect on phospho-CaMKII levels during acute stress. Neither acute nor chronic stress changed mRNA levels of NMDA and AMPA receptors. These results demonstrate that immobilization stress promotes the phosphorylation of CaMKII. The increase in the intracellular Ca2+ concentration by the activation of AMPA receptors may play a role in the stress-induced phospho-CaMKII in the rat hippocampus.