Yang Z J, Rao Z R, Ju G
Institute of Neurosciences, Fourth Military Medical University, Shaanxi Province, Xi'an, 710032, People's Republic of China.
Neurosci Res. 2000 Nov;38(3):237-47. doi: 10.1016/s0168-0102(00)00165-6.
The aim of the present study was to test the possibility that the catecholaminergic projectional pathway from the vagus nerve to the medullary visceral zone (MVZ) thence to the paraventricular nucleus of hypothalamus (PVN) was involved in the cytokine-to-brain communication. A triple labeling method in which WGA-HRP retrograde tracing was combined with anti-Fos and -TH immunohistochemical staining was used. WGA-HRP was stereotaxically injected into unilateral PVN in the rat, after a survival of 48 h, animals received intraperitoneal injection of lipopolysaccharide (LPS). The distribution of the HRP retrogradely labeled neurons, Fos protein positive and catecholaminergic neurons (tyrosine hydroxylase as marker) in the MVZ was observed. Subdiaphragmatic vagotomy (SDV) and sham surgery were also used to observe the different Fos expression in the MVZ after intraperitoneal administration of lipopolysaccharide (LPS) or pyrogen-free saline (NS). Under light microscope, seven types of positively stained neurons could be distinguished within the MVZ, namely neurons single-labeled with Fos, HRP or TH, respectively; neurons double-labeled with Fos/TH, Fos/HRP or HRP/TH separately; and neurons triple-labeled with Fos, HRP and TH staining. Intraperitoneal LPS caused lots of robust Fos expression within the MVZ in the sham surgery groups and this response in the MVZ was markedly inhibited in the vagotomized rats. The results suggested that some catecholaminergic neurons in the MVZ could send projections to the PVN and this pathway might be involved in the relay of peripheral immune information via vagus nerve. MVZ was a neural relay station in the immune-to-brain communication and might play a significant role in the neuroimmunomodulation via vagus-MVZ-PVN pathway.
本研究的目的是检验从迷走神经到延髓内脏区（MVZ）进而到下丘脑室旁核（PVN）的儿茶酚胺能投射通路是否参与细胞因子与脑的通讯。采用了一种三重标记方法，即将WGA-HRP逆行追踪与抗Fos和抗TH免疫组织化学染色相结合。将WGA-HRP立体定位注射到大鼠的单侧PVN中，在存活48小时后，动物接受腹腔注射脂多糖（LPS）。观察MVZ中HRP逆行标记神经元、Fos蛋白阳性神经元和儿茶酚胺能神经元（以酪氨酸羟化酶为标记）的分布。还采用膈下迷走神经切断术（SDV）和假手术来观察腹腔注射脂多糖（LPS）或无热原生理盐水（NS）后MVZ中不同的Fos表达。在光学显微镜下，MVZ内可区分出七种阳性染色神经元，即分别用Fos、HRP或TH单标记的神经元；分别用Fos/TH、Fos/HRP或HRP/TH双标记的神经元；以及用Fos、HRP和TH染色三重标记的神经元。腹腔注射LPS在假手术组的MVZ中引起大量强烈的Fos表达，而在迷走神经切断的大鼠中MVZ的这种反应明显受到抑制。结果表明，MVZ中的一些儿茶酚胺能神经元可以向PVN投射，并且该通路可能参与通过迷走神经传递外周免疫信息。MVZ是免疫与脑通讯中的一个神经中继站，可能在通过迷走神经-MVZ-PVN通路的神经免疫调节中发挥重要作用。
