Background Determining the etiology and possible treatment strategies for numerous diseases requires a comprehensive understanding of compensatory mechanisms in physiological systems. The vagus nerve acts as a key interface between the brain and the peripheral internal organs. We set out to identify mechanisms compensating for a lack of neuronal communication between the immune and the central nervous system (CNS) during infection. Methods We assessed biochemical and central neurotransmitter changes resulting from subdiaphragmatic vagotomy and whether they are modulated by intraperitoneal infection. We performed a series of subdiaphragmatic vagotomy or sham operations on male Wistar rats. Next, after full, 30-day recovery period, they were randomly assigned to receive an injection of Escherichia coli lipopolysaccharide or saline. Two hours later, animal were euthanized and we measured the plasma concentration of prostaglandin E2 (with HPLC-MS), interleukin-6 (ELISA), and corticosterone (RIA). We also had measured the concentration of monoaminergic neurotransmitters and their metabolites in the amygdala, brainstem, hippocampus, hypothalamus, motor cortex, periaqueductal gray, and prefrontal medial cortex using RP-HPLC-ED. A subset of the animals was evaluated in the elevated plus maze test immediately before euthanization. Results The lack of immunosensory signaling of the vagus nerve stimulated increased activity of discrete inflammatory marker signals, which we confirmed by quantifying biochemical changes in blood plasma. Behavioral results, although preliminary, support the observed biochemical alterations. Many of the neurotransmitter changes observed after vagotomy indicated that the vagus nerve influences the activity of many brain areas involved in control of immune response and sickness behavior. Our studies show that these changes are largely eliminated during experimental infection. Conclusions Our results suggest that in vagotomized animals with blocked CNS, communication may transmit via a pathway independent of the vagus nerve to permit restoration of CNS activity for peripheral inflammation control.
Wymiana informacji pomiędzy wzbudzonym układem odpornościowym a ośrodkowym układem nerwowym (OUN) zapewnia utrzymanie stanu homeostazy organizmu. Jedną z głównych dróg odpowiedzialnych za wspomnianą komunikację jest droga humoralna. Reprezentują ją związki uwalniane przez komórki odpornościowe oraz uszkodzone tkanki. Cząsteczkami istotnie zaangażowanymi we wspomniany proces komunikacji są prostaglandyny, szczególnie prostaglandyna E2 (PGE2), powstająca w wyniku aktywności cyklooksygenaz. Posiada szereg właściwości umożliwiających penetrację barier organizmu, w tym bariery krew-mózg, co więcej w OUN potwierdzono obecność specyficznych dla niej receptorów. Za ich pośrednictwem, PGE2 moduluje aktywność układów neurotransmisyjnych w OUN, co w konsekwencji indukuje złożone mechanizmy odpornościowe organizmu. Ostatecznie dochodzi do skutecznej neutralizacji infekcji przy jednoczesnym hamowaniu aktywności nadmiernie wzbudzonego układu odpornościowego. Efekty wywoływane przez PGE2 ulegają osłabieniu lub całkowitemu zniesieniu poprzez zastosowanie określonych inhibitorów cyklooksygenaz. Niniejsza praca stanowi podsumowanie obecnych wiadomości dotyczących procesów wymiany informacji pomiędzy wzbudzonym układem odpornościowym a OUN za pośrednictwem PGE2.
In the central nervous system, long‑term effects of a vagotomy include disturbance of monoaminergic activity of the limbic system. Since low vagal activity is observed in major depression and autism spectrum disorder, the study aimed to determine whether animals fully recovered after subdiaphragmatic vagotomy demonstrates neurochemical indicators of altered well‑being and social component of sickness behavior. Bilateral vagotomy or sham surgery was performed in adult rats. After one month of recovery, rats were challenged with lipopolysaccharide or vehicle to determine the role of central signaling upon sickness. Striatal monoamines and met‑enkephalin concentrations were evaluated using HPLC and RIA methods. We also defined a concentration of immune‑derived plasma met‑enkephalin to establish a long‑term effect of vagotomy on peripheral analgesic mechanisms. The data indicate that 30 days after vagotomy procedure, striatal dopaminergic, serotoninergic, and enkephalinergic neurochemistry was altered, both under physiological and inflammatory conditions. Vagotomy prevented inflammation‑induced increases of plasma met‑enkephalin – an opioid analgesic. Our data suggest that in a long perspective, vagotomized rats may be more sensitive to pain and social stimu li during peripheral inflammation.
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