Antidepressant-mediated reversal of abnormal behavior and neurodegeneration in mice following olfactory bulbectomy
Antidepressant-mediated reversal of abnormal behavior and neurodegeneration in mice following olfactory bulbectomy
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DOI：
10.1016/j.expneurol.2006.09.008
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发表时间：
2007-03-01
影响因子：
5.3
通讯作者：
von Bohlen und Halbach, Oliver
中科院分区：
文献类型：
--
作者：
Jarosik, J.;Legutko, B.;von Bohlen und Halbach, Oliver
嗅球切除术是一种已建立的抑郁症动物模型，在大鼠中研究最多。在人类重度抑郁症中，球根切除术会引起行为改变，这种改变可以通过慢性抗抑郁治疗得到改善。此外，已知大鼠的球根切除术可诱导某些脑区神经变性。本研究的目的是评估行为改变和神经变性的模式，及其药物诱导的可逆性，在球切除小鼠。我们的研究结果表明，在小鼠中，球部切除术增加了运动活动并诱导被动回避测试的缺陷，与在大鼠中看到的效果相当。在梨状皮质和后外侧皮质杏仁核（PLCo）中，球切术也诱导神经元变性。抗抑郁药物阿米替林的长期治疗保护了这两个区域的神经元，并有效地逆转了球根切除引起的异常运动活动。用西酞普兰治疗可有效逆转球根切除引起的行为缺陷，但不能防止神经退行性变。我们的数据表明，小鼠和大鼠在嗅球切除术后的行为改变和神经变性方面有显著的重叠。然而，药物介导的神经变性可逆性存在差异，这表明神经变性和保护可能是抑郁症动物模型的“二级”特征。这也可能与使用转基因小鼠的研究有关。(c) 2006爱思唯尔公司版权所有。
Olfactory bulbectomy is an established animal model of depression that has been mostly investigated in rats. As in human major depression, bulbectomy induces behavioral alterations that can be ameliorated by chronic antidepressant treatment. Furthermore, bulbectomy in rats is known to induce neurodegeneration in some brain areas. The aim of the present study was to evaluate patterns of behavioral alterations and neurodegeneration, and their drug-induced reversibility, in bulbectomized mice. Our results reveal that in mice bulbectomy increases locomotor activity and induces deficits in the passive avoidance test, comparable to the effects seen in rats. Bulbectomy also induced neuronal degeneration, visualized by incorporation of Fluoro-Jade B, in the piriform cortex and the posterolateral cortical amygdaloid nucleus (PLCo). Chronic treatment with the antidepressant amitriptyline protected neurons in both areas and efficiently reversed abnormal locomotor activity induced by bulbectomy. Treatment with citalopram was effective in reversing the behavioral deficits induced by bulbectomy, but did not protect against neurodegeneration. Our data indicate significant overlap between mice and rats in terms of behavioral alterations and neurodegeneration following olfactory bulbectomy. However, there are differences in drug-mediated reversibility of neurodegeneration suggesting that neurodegeneration and protection may be "second-order" features in this animal model of depression. This may also be relevant in the context of studies using genetically altered mice. (c) 2006 Elsevier Inc. All rights reserved.