Fluoxetine modulates hippocampal cell signaling pathways implicated in neuroplasticity in olfactory bulbectomized mice
Fluoxetine modulates hippocampal cell signaling pathways implicated in neuroplasticity in olfactory bulbectomized mice
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DOI：
10.1016/j.bbr.2012.09.035
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发表时间：
2013-01-15
影响因子：
2.7
通讯作者：
Rodrigues, Ana Lucia S.
中科院分区：
文献类型：
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作者：
Freitas, Andiara E.;Machado, Daniele G.;Rodrigues, Ana Lucia S.
抑郁症的嗅球切除术（OB）动物模型是一种成熟的模型，其能够检测慢性药物治疗后的抗抑郁活性，并且手术导致使人联想到抑郁症的各种症状的行为和生化变化。在本研究中，我们调查了14天的p.o.施用经典的抗抑郁药氟西汀（10 mg/kg）能够逆转OB诱导的行为变化（即，在旷场试验中的活动过度和在飞溅试验中的动机和自我护理行为减少）和被认为参与突触可塑性的海马细胞信号传导途径的激活。OB引起ERK 1和CREB（Ser（133））磷酸化和BDNF免疫含量表达的显著增加，所有这些都被氟西汀给药所阻止。此外，氟西汀给药还导致OB小鼠ERK 2磷酸化水平显著降低。Akt和GSK-3 β磷酸化在任何实验条件下都没有改变。总之，本研究表明OB可以诱导显着的行为变化，并伴有海马信号通路的激活，即参与突触可塑性的ERK 1/CREB/BDNF通路。相反，氟西汀阻止了这些OB诱导的行为变化，并避免了海马中ERK 1/CREB/BDNF的激活。总之，我们的研究结果扩展了现有文献中关于OB诱导的行为和神经化学变化的数据，并提出了一种可能的潜在机制，可以解释氟西汀在该模型中的抗抑郁作用。(C)2012爱思唯尔有限公司版权所有。
The olfactory bulbectomy (OB) animal model of depression is a well-established model that is capable of detecting antidepressant activity following chronic drug therapy, and the surgery results in behavioral and biochemical changes that are reminiscent of various symptoms of depression. In the present study, we investigated the degree to which 14 days of p.o. administration of the classic antidepressant fluoxetine (10 mg/kg) were able to reverse OB-induced changes in behavior (namely, hyperactivity in the open-field test and reduced motivational and self-care behaviors in the splash test) and in the activation of hippocampal cell signaling pathways that are thought to be involved in synaptic plasticity. OB caused significant increases in ERK1 and CREB (Ser(133)) phosphorylation and in the expression of BDNF immunocontent, all of which were prevented by fluoxetine administration. Moreover, fluoxetine administration also caused a significant decrease in ERK2 phosphorylation in mice that had undergone OB. Neither Akt nor GSK-3 beta phosphorylation was altered in any experimental condition. In conclusion, the present study shows that OB can induce significant behavioral changes that are accompanied by the activation of hippocampal signaling pathways, namely the ERK1/CREB/BDNF pathway, which is involved in the synaptic plasticity. Conversely, fluoxetine prevented these OB-induced behavioral changes and avoided the activation of ERK1/CREB/BDNF in the hippocampus. Taken together, our results extend the data from the existing literature regarding OB-induced behavioral and neurochemical changes, and suggest a possible underlying mechanism that can account for the antidepressant effect of fluoxetine in this model. (C) 2012 Elsevier B.V. All rights reserved.