Impaired fear memory and decreased hippocampal neurogenesis following olfactory bulbectomy in rats

Impaired fear memory and decreased hippocampal neurogenesis following olfactory bulbectomy in rats
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DOI:
10.1111/j.1460-9568.2005.04481.x
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发表时间:
2005-12-01
影响因子:
3.4
通讯作者:
Zharkovsky, A
Zharkovsky, A
中科院分区:
医学3区
文献类型:
--
作者:
Jaako-Movits, K;Zharkovsky, A

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已经提出,成年海马神经发生的减少为重度抑郁症提供了生物学和细胞学基础。大鼠嗅球切除术(olfactory bulbectomy,OB)是一种公认的抑郁症动物模型。本研究探讨了OB对海马功能和成年海马神经发生相关记忆任务中记忆形成的影响。OB诱导的行为综合征,其特征是增加活动的开放领域的测试和减值的被动回避行为和上下文的恐惧条件反射。OB后的行为变化伴随着齿状回增殖细胞数量的减少。此外,新生细胞向成熟钙结合蛋白阳性神经元的分化也受到阻碍。体视学分析显示齿状回颗粒细胞层内的颗粒神经元总数减少,而齿状回体积没有显著减少。虽然OB引起的神经发生改变和行为综合征之间的关系尚未建立,但我们的研究结果表明,神经发生减少可能至少部分导致OB后的行为缺陷。
It has been proposed that a decrease in adult hippocampal neurogenesis provides a biological and cellular basis for major depression. The olfactory bulbectomy (OB) in rats is widely accepted as an animal model of depression. In the present study, we investigated the effect of OB on memory formation in the memory tasks related to the hippocampal function and adult hippocampal neurogenesis. OB induced a behavioural syndrome, which was characterized by an increased activity in the open-field test and impairment in passive avoidance behaviour and contextual fear conditioning. The behavioural changes, following OB, were accompanied by a decrease in the number of proliferating cells in the dentate gyrus. Furthermore, the differentiation of the newly born cells, into mature calbindin-positive neurons, was also retarded. Stereological analysis revealed a decrease in the total granule neuron numbers within the granule cell layer of the dentate gyrus, without a significant decrease in volume of the dentate gyrus. Although a relationship between altered neurogenesis and behavioural syndrome, induced by OB, is not established yet, our results suggest that decreased neurogenesis might at least partly contribute for behavioural deficits following OB.