Cytoskeletal changes in the hippocampus following restraint stress: Role of serotonin and Microtubules
Cytoskeletal changes in the hippocampus following restraint stress: Role of serotonin and Microtubules
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DOI：
10.1002/syn.10230
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发表时间：
2003-09-01
期刊：
影响因子：
2.3
通讯作者：
Crespi, F
中科院分区：
文献类型：
--
作者：
Bianchi, M;Heidbreder, C;Crespi, F
抑郁症的病因与中枢5-羟色胺（5-HT）水平的耗竭有关。因此，抗抑郁药物的主要作用是增加突触5-HT水平。应激条件也被证明会影响海马中的神经元可塑性和5-HT神经传递。神经元可塑性通常被称为神经元对功能要求的结构适应，需要更多动态形式的微管（细胞骨架成分）。微管蛋白是微管的主要成分，可以被翻译后修饰，酪氨酸化（tyr-tub）和乙酰化（acet-tub）形式分别被认为是更动态或更稳定的微管的标志物。本工作的目的是研究急性（6 h，1 d）或亚慢性（6 h，4 d，每天）束缚应激大鼠海马中tyr-tub和acet-tub的表达。此外，离体海马5-HT水平进行了监测，通过差分脉冲伏安法分析的影响，这两种压力条件后5-HT水平。结果表明，在亚慢性束缚应激后，海马中Tyr-tub的表达显著降低至70 ± 7%（P < 0.01）。相比之下，急性和亚慢性束缚应激分别使海马acet-tub的表达增加到对照组的139 +/- 11%和145 +/- 11%。最后，在急性和亚慢性束缚应激后，5-HT水平分别显著增加（P < 0.05）至142 +/- 15%和135 +/- 11%。本研究中观察到的应激诱导的细胞骨架变化表明，微管网络是一个潜在的新途径，可能会增加我们对应激相关事件的理解。(C)2003 Wiley-Liss，Inc.
The aetiology of depression is associated with depletion in central levels of serotonin (5-HT). Hence, a major effect of antidepressant drugs is to increase synaptic 5-HT levels. Stressful conditions have also been shown to affect neuronal plasticity and 5-HT neurotransmission in the hippocampus. Neuronal plasticity, which is typically referred to as a structural adaptation of neurons to functional requirements, requires more dynamic forms of microtubules (cytoskeletal component). The a-tubulin, which is the major component of microtubules, can be postranslationally modified and both the tyrosinated (tyr-tub) and acetylated (acet-tub) forms are considered markers of more dynamic or more stable microtubules, respectively. The aim of the present work was to investigate the expression of tyr-tub and acet-tub in the hippocampus of rats submitted to either acute (6 h for 1 day) or sub-chronic (6 h for 4 days every day) restraint stress. In addition, ex vivo hippocampal 5-HT levels were monitored by differential pulse voltammetry to analyse the influence of both stress conditions upon 5-HT levels. Our results showed that the expression of tyr-tub in the hippocampus was significantly decreased to 70 +/- 7% following sub-chronic restraint stress (P < 0.01). In contrast, acute and sub-chronic restraint stress increased the hippocampal expression of acet-tub to 139 +/- 11% and 145 +/- 11% of control, respectively. Finally, 5-HT levels were significantly increased (P < 0.05) to 142 +/- 15% and 135 +/- 11% following acute and sub-chronic restraint stress, respectively. The stress-induced cytoskeletal changes observed in the present study suggest that the microtubular network is a potential new pathway that may increase our understanding of stress-related events. (C) 2003 Wiley-Liss, Inc.