A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior
A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior
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DOI：
10.1016/j.bbr.2008.11.051
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发表时间：
2009-05-16
影响因子：
2.7
通讯作者：
Sun, Meng
中科院分区：
文献类型：
--
作者：
Qi, Xiaoli;Lin, Wenjuan;Sun, Meng
我们最近的研究表明，细胞外信号调节激酶（ERK）信号通路在抑郁症动物中受损，这种破坏在抗抑郁药治疗后被有效逆转。这些结果表明ERK通路可能参与了抑郁症的分子机制。为了提供ERK通路在抑郁症中的潜在作用的直接证据，本研究使用ERK抑制的亚慢性方案调查了ERK级联在两个特定脑区，背海马（dHP）和内侧前额叶皮层（mPFC）的不同作用。抑郁症样行为的病理生理学。大鼠双侧植入套管在dHP或mPFC和微量注射U0126，ERK上游激活剂的特异性抑制剂，或车辆连续7天。采用旷场、高架十字迷宫和糖精偏爱实验检测ERK通路抑制对大鼠行为学的影响。结果表明，dHP中ERK通路的抑制导致大鼠快感缺乏和焦虑样行为，mPFC中ERK通路的抑制导致大鼠快感缺乏和运动障碍。在dHP或mPFC中，ERK通路抑制后，环AMP反应元件结合蛋白（CREB）的磷酸化水平降低。这些发现表明，dHP或mPFC中的ERK通路参与了抑郁样行为的病理生理学，并且可能在人类抑郁症中发挥关键作用。(C)2008 Elsevier B.V.保留所有权利。
Our recent research demonstrates that the extracellular signal-regulated kinase (ERK) signal pathway is impaired in depressed animals, and such disruption is effectively reversed following antidepressant treatment. These results indicate that the ERK pathway may participate in the molecular mechanism of depression. To provide direct evidence for the potential role of the ERK pathway in depression, the present study using a sub-chronic regimen of ERK inhibition investigated the disparate role for the ERK cascade in two specific brain areas, the dorsal hippocampus (dHP) and the medial prefrontal cortex (mPFC). in the pathophysiology of depressive-like behavior. Rats were bilaterally implanted with cannulas in the dHP or mPFC and were microinjected with U0126, a specific inhibitor of ERK upstream activator, or vehicle for 7 consecutive days. The behavioral effects of the ERK pathway inhibition were examined in the open field, elevated plus maze, and saccharin preference test. The results showed that the inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats. The phosphorylation of the cyclic AMP-responsive-element-binding protein (CREB) was decreased following the ERK pathway inhibition either in dHP or mPFC. These findings demonstrate that the ERK pathway in either the dHP or mPFC participates in the pathophysiology of the depressive-like behavior, and may have pivotal role in human depression. (C) 2008 Elsevier B.V. All rights reserved.