Role of newly found brain stem neuropeptide on exercise-induced stress response and performance.

当速度超过乳酸阈值（LT）时，跑步刺激ACTH释放，血乳酸积累的断点似乎在最大摄氧量的50-60%左右，定义为跑步压力。尽管跑步诱导ACTH反应的确切脑机制尚不清楚，但投射到下丘脑室旁核的腹外延髓（VLM）和孤立束核（NTS）在调节跑步应激中可能起着至关重要的作用。催乳素释放肽（PrRP）是近年来分离到的一种由VLM、NTS和下丘脑背内侧核产生的物质。脑室内给予PrRP刺激ACTH释放，应激条件下PrRP神经元Fos蛋白积累增加，提示PrRP神经元在运行应激诱导ACTH反应中起作用。首先，我们之前发现含有PrRP的A1去甲肾上腺素神经元中Fos蛋白的积累取决于跑步速度，尤其是在LT以上（Exp.1）。在Exp.2中，我们首先发现Fos积累随着跑步速度的增加而增加（Exp.2）。此外，我们发现脑PrRP的免疫中和使用icv给药与PrRP单克隆抗体显著提高ACTH和血乳酸水平，以响应运行应激（见表3）。相反，低剂量PrRP （1nmol）灌胃治疗与免疫中和治疗效果相反（实验结果4）。这表明PrRP通过对中枢神经系统的抑制作用部分介导ACTH对跑步压力的释放反应。在实验5中，我们假设PrRP降低血乳酸和ACTH反应的神经元机制可能是通过抑制下丘脑AVP神经元，特别是抑制室旁核（pPVN）和视上核（SON）中的AVP神经元来发挥作用的。结果表明，低剂量PrRP （1nmol）可显著降低运动应激下ppvn和SON-AVP阳性神经元Fos的积累。目前的研究结果表明，脑PrRP通过作用于下丘脑来抑制运动应激诱导的乳酸和ACTH反应：抑制作用作用于ppvn和SON-AVP神经元。因此，我们提出了一个新的假设，即PrRP可能在维持高运动消耗方面发挥重要作用。少

Running stimulates ACTH release when speed is beyond the lactate threshold (LT), the breakpoint for blood lactate accumulation appears to be around 50-60% of maximal oxygen uptake, defined as running stress. Although the exact brain mechanism underlying the running-induced ACTH response is unknown, the ventrolateral medulla (VLM) and the nucleus of the solitary tract (NTS) that project to the hypothalamic paraventricular nucleus would have crucial role in regulating running stress. Prolactin releasing peptide (PrRP) was recently isolated and found to be produced by the VLM, NTS and dorsomedial hypothalamic nucleus. Intracerebroventricular administration of PrRP stimulates ACTH release and the Fos protein accumulation in PrRP neurons increased under stress conditions suggest that PrRP neurons play a role in running stress-induced ACTH response. First, we previously found that Fos protein accumulation in A1 noradrenaline neurons that contain PrRP increased depends on running speed, espec … More ially just above the LT (Exp.1). In the Exp.2, first we found that Fos accumulation increased depend on running speed (Exp.2). Further, we found that immunoneutralization of brain PrRP with use of icv administration with monoclonal antibody for PrRP significantly enhances ACTH and blood lactate levels increases in response to running stress (Exp.3). On the contrary, i.c.v. treatment with low dose of PrRP (1nmol) caused opposite effects than that of the immunoneutralization (Exp.4). This shows PrRP partially mediates ACTH release response to running stress through inhibitory action on the central nervous system. In the Exp.5, we hypothesized that this neuronal mechanism by which PrRP reduces blood lactate and ACTH responses would be exerted via inhibitory action on the hypothalamic AVP neurons, especially in the AVP neurons in the parvocellular paraventricular nucleus (pPVN) and supraoptic nucleus (SON). As the results, if administered (icv) low dose of PrRP (1nmol) caused dramatic decrease in Fos accumulation in the pPVN-and SON-AVP positive neurons in response to running stress. The present results suggest that brain PrRP suppress the running stress-induced lactate and ACTH responses by acting in the hypothalamus : the inhibitory action was exerted in the pPVN-and SON-AVP neurons. Thus, we thus propose a new hypothesis that PrRP may have a significant role to maintain the expenditure of exercise to be high. Less