Evidence for involvement of the neural pathway containing the peripheral vagus nerve, medullary visceral zone and central amygdaloid nucleus in neuroimmunomodulation

It is now evident that a bidirectional communication network exists between the central nervous system (CNS) and immune system (IS). However, the way in which the IS passes inform to the brain is not quite clear. In the prese nt study, one of the neural pathways involved in the cytokine-to-brain comm unication was investigated in the rat. This pathway starts at the vagal ner ve projecting to the medullary visceral zone (MVZ), an arc-shape band from the dorsomedial to ventrolateral area in the middle-caudal segment of the m edulla oblongata, and terminates at the central amygdaloid nucleus (Cc) whi ch receives projections from large catecholaminergic neurons in the MVZ. An imals were randomly divided into two experimental groups. Triple-labeling w as used in Group I animals to combine wheat germ aggulutinin-conjugated hor seradish peroxidase (WGA-HRP) retrograde tracing with anti-Fos and anti-tyr osine hydroxylase (TH) immunostaining. WGA-RP was stereotaxically injected into the unilateral Cc of the animals and, after a survival period of 48 h, intraperitoneal (IP) injection of lipopolysaccharide (LPS) was performed. Seven kinds of labeled neurons were observed in the MVZ, namely, HRP-, Fos- or TH-singly-labeled neurons; Fos/HRP-, Fos/TH- or HRP/TH-doubly-labeled n eurons; and Fos/HRP/TH-triply-labeled neurons. As for Group II animals, bil ateral subdiaphragmatic vagotomy (SDV) or sham operation was performed, fol lowed 4 weeks later by IP injection of LPS. The number of Fos-positive neur ons within the Cc and MVZ was significantly lower (P <0.01) in rats having SDV when compared with those receiving sham operation. Our results suggest that part of the peripheral immune information can be conveyed through the vagus to the catecholaminergic neurons in the MVZ, where it is transported to the Cc. The MVZ is a neural relay station in the immune-to-brain communi cation and might play a significant role in neuroimmuno-modulation via the vagus-MVZ-Ce pathway. (C) 2001 Published by Elsevier Science B.V.