Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
J Physiol. 2011 Sep 15;589(Pt 18):4457-71. doi: 10.1113/jphysiol.2011.210245. Epub 2011 Jun 27.
We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2-3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT(1) receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t)SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla-spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e.g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EH rats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration.
我们研究了在体内和原位标本中，2-3 天脱水（DH）引起血压升高和交感神经活动（SNA）增加的机制。在正常水合（EH）大鼠中，全身应用 AT(1)受体拮抗剂 Losartan 并随后进行前脑桥切断术（切除下丘脑）可显著降低胸段（t）SNA。相比之下，在 DH 大鼠中，Losartan 随后进行前脑桥和脑桥切断术，未能降低 tSNA，而在延髓-脊髓交界处进行切断术则大量降低 tSNA。在 DH 但不是 EH 大鼠中，选择性抑制连合核孤束核（cNTS）显著降低 tSNA。在原位和体内（麻醉/清醒）大鼠中均获得了类似的数据，并表明在慢性脱水后，tSNA 的控制从脑桥以上结构（例如下丘脑）转移到延髓，特别是 cNTS。由于微阵列分析显示脱水 cNTS 中 AP1 转录因子 JunD 的上调，我们测试了 AP1 转录因子活性负责脱水诱导的功能可塑性的假设。当使用表达显性负 FosB 的病毒载体阻断 cNTS 中的 AP1 转录因子活性时，cNTS 失活无效。然而，在前脑桥切断术后，tSNA 减少，这与 EH 大鼠的反应相似。因此，从下丘脑到 cNTS 的 tSNA 控制的脱水诱导转换似乎是通过激活 cNTS 中的 AP1 转录因子介导的。如果在脱水期间在 cNTS 中阻断 AP1 活性，交感神经活动控制会恢复到前脑区域。这种大脑中心之间的独特往复神经结构转换可塑性强调了适应脱水的多种可用机制。
