Upregulation of brain-derived neurotrophic factor expression in nodose ganglia and the lower brainstem of hypertensive rats.
Upregulation of brain-derived neurotrophic factor expression in nodose ganglia and the lower brainstem of hypertensive rats.
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DOI：
10.1002/jnr.23158
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发表时间：
2013-02
影响因子：
4.2
通讯作者：
Balkowiec, Agnieszka
中科院分区：
文献类型：
--
作者：
Vermehren-Schmaedick, Anke;Jenkins, Victoria K.;Hsieh, Hui-ya;Brown, Alexandra L.;Page, Mollie P.;Brooks, Virginia L.;Balkowiec, Agnieszka
高血压导致内侧孤束核（NTS）压力感受器突触的结构和功能变化，但潜在的分子机制仍不清楚。我们之前的研究表明，脑源性神经营养因子（BDNF）在大鼠结状神经节（NG）神经元中大量表达，包括压力感受器传入神经及其内侧 NTS 的中枢末梢。我们假设高血压导致 NG 神经元中 BDNF 表达上调。为了检验这一假设，我们使用了两种机制不同的高血压模型：自发性高血压大鼠（SHR）和醋酸脱氧皮质酮（DOCA）盐大鼠。与年龄匹配的 Wistar-Kyoto (WKY) 对照大鼠相比，年轻成年 SHR 的血压显着升高，并表现出 NG 中 BDNF mRNA 和蛋白质的显着上调。已知受活性调节的外显子 4 和外显子 9（蛋白质编码区）的 BDNF 转录物显示出最大的增加。以模拟血压升高期间压力感受器活动的模式对分散的 NG 神经元进行电刺激，导致 BDNF mRNA 增加，这也是通过启动子 4 介导的。体内 NG BDNF 含量的增加与 BDNF 免疫反应性 NG 神经元百分比的显着增加相关。此外，NG 神经元细胞体中 BDNF 的上调伴随着 NTS 区域（NG 传入神经的主要中心目标）中 BDNF 的显着增加。在 DOCA 盐高血压大鼠中也检测到 NG 中 BDNF 的显着增加。总之，我们的研究将 BDNF 确定为高血压期间压力传入突触活动依赖性变化的候选分子介质。
Hypertension leads to structural and functional changes at baroreceptor synapses in the medial nucleus tractus solitarius (NTS), but the underlying molecular mechanisms remain unknown. Our previous studies show that brain-derived neurotrophic factor (BDNF) is abundantly expressed by rat nodose ganglion (NG) neurons, including baroreceptor afferents and their central terminals in the medial NTS. We hypothesized that hypertension leads to upregulation of BDNF expression in NG neurons. To test this hypothesis, we used two mechanistically distinct models of hypertension: the spontaneously hypertensive rat (SHR) and the deoxycorticosterone acetate (DOCA)-salt rat. Young adult SHRs, whose blood pressure was significantly elevated compared to age-matched Wistar-Kyoto (WKY) control rats, exhibited dramatic upregulation of BDNF mRNA and protein in the NG. BDNF transcripts from exon 4, known to be regulated by activity, and exon 9 (protein-coding region) showed the largest increases. Electrical stimulation of dispersed NG neurons with patterns that mimic baroreceptor activity during blood pressure elevations led to increases in BDNF mRNA that were also mediated through promoter 4. The increase in BDNF content of the NG in vivo was associated with a significant increase in the percentage of BDNF-immunoreactive NG neurons. Moreover, upregulation of BDNF in cell bodies of NG neurons was accompanied by a significant increase in BDNF in the NTS region, the primary central target of NG afferents. A dramatic increase in BDNF in the NG was also detected in DOCA-salt hypertensive rats. Together, our study identifies BDNF as a candidate molecular mediator of activity-dependent changes at baroafferent synapses during hypertension.
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DOI：
10.1152/ajpregu.00068.2006
发表时间：
2006-12-01
影响因子：
2.8
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
1999-10-01
影响因子：
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DOI：
10.1046/j.1440-1681.2001.03567.x
发表时间：
2001-12-01
影响因子：
2.9
作者：
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