Induction of c-fos and ΔFosB immunoreactivity in rat brain by vagal nerve stimulation
Induction of c-fos and ΔFosB immunoreactivity in rat brain by vagal nerve stimulation
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DOI：
10.1038/sj.npp.1301570
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发表时间：
2008-07-01
影响因子：
7.6
通讯作者：
Frazer, Alan
中科院分区：
文献类型：
--
作者：
Cunningham, J. Thomas;Mifflin, Steven W.;Frazer, Alan
迷走神经刺激（VNS）被用作难治性抑郁症或癫痫的治疗。本研究使用免疫组织化学的短期（c-Fos）和长期（Delta FosB）神经元激活的生物标志物，以映射在清醒的Sprague-Dawley大鼠中由急性（2小时）或慢性（3周）VNS激活的大脑区域。电极（Cyberonics Inc.）植入左侧迷走神经，手术后1周，使用临床使用的参数开始刺激（每5分钟一次20 Hz，250 μ s脉冲宽度，0.25 mA刺激30 s）。无线电遥测发射器用于监测血压，心率，活动，呼吸频率在VNS;急性或慢性VNS显着影响这些参数。急性迷走神经刺激可使孤束核、下丘脑室旁核、臂旁核、终纹腹侧床核和蓝斑核的c-Fos染色显著增强，但在扣带皮层和中缝背核（DRN）的c-Fos染色不明显。急性VNS不影响任何区域的Delta FosB染色。慢性VNS显著增加三角洲FosB和c-Fos染色双边在每个地区受到急性VNS以及在扣带皮层和DRN。使用这些刺激参数，使用强迫游泳试验（FST）测试VNS的抗抑郁样活性。VNS和地昔帕明显着降低不动性在FST，而地昔帕明减少不动性增加攀爬行为，VNS这样做，增加游泳行为。这项研究，然后，确定了潜在的网站在大脑中的VNS可能产生其临床效果。
Vagus nerve stimulation (VNS) is used as therapy for treatment-resistant depression or epilepsy. This study used immunohistochemistry for biomarkers of short-term (c-Fos) and long-term (Delta FosB) neuronal activation to map regions in brain that are activated by acute (2 h) or chronic (3 weeks) VNS in conscious Sprague-Dawley rats. Electrodes (Cyberonics Inc.) were implanted on the left vagus nerve and 1 week after surgery, stimulation began using parameters employed clinically (one burst of 20 Hz, 250 mu s pulse width, 0.25 mA stimulation for 30 s every 5 min). Radio telemetry transmitters were used for monitoring blood pressure, heart rate, activity, and respiratory rate during VNS; neither acute nor chronic VNS significantly affected these parameters. Acute VNS significantly increased c-Fos staining in the nucleus of the solitary tract, paraventricular nucleus of the hypothalamus, parabrachial nucleus, ventral bed nucleus of the stria terminalis, and locus coeruleus but not in the cingulate cortex or dorsal raphe nucleus (DRN). Acute VNS did not affect Delta FosB staining in any region. Chronic VNS significantly increased Delta FosB and c-Fos staining bilaterally in each region affected by acute VNS as well as in the cingulate cortex and DRN. Using these stimulation parameters, VNS was tested for antidepressant-like activity using the forced swim test (FST). Both VNS and desipramine significantly decreased immobility in the FST; whereas desipramine decreased immobility by increasing climbing behavior, VNS did so by increasing swimming behavior. This study, then, identified potential sites in brain where VNS may produce its clinical effects.