Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation
Abstract 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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-07-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-019-1544-y |
| _version_ | 1818215911662813184 |
|---|---|
| author | Anna Kobrzycka Paweł Napora Brandon L. Pearson Krystyna Pierzchała-Koziec Rafał Szewczyk Marek Wieczorek |
| author_facet | Anna Kobrzycka Paweł Napora Brandon L. Pearson Krystyna Pierzchała-Koziec Rafał Szewczyk Marek Wieczorek |
| author_sort | Anna Kobrzycka |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T06:43:36Z |
| format | Article |
| id | doaj.art-b34a9bbbcdec4936b1d839407675409c |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-12T06:43:36Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-b34a9bbbcdec4936b1d839407675409c2022-12-22T00:34:16ZengBMCJournal of Neuroinflammation1742-20942019-07-0116111810.1186/s12974-019-1544-yPeripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activationAnna Kobrzycka0Paweł Napora1Brandon L. Pearson2Krystyna Pierzchała-Koziec3Rafał Szewczyk4Marek Wieczorek5Department of Neurobiology, Faculty of Biology and Environmental Protection, University of LodzDepartment of Neurobiology, Faculty of Biology and Environmental Protection, University of LodzDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia UniversityDepartment of Animal Physiology and Endocrinology, University of AgricultureDepartment of Industrial Microbiology and Biotechnology, Faculty of Biology and Environmental Protection, University of LodzDepartment of Neurobiology, Faculty of Biology and Environmental Protection, University of LodzAbstract 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.http://link.springer.com/article/10.1186/s12974-019-1544-yVagus nerveVagotomyProstaglandin E2PGE2Compensatory mechanismsCNS communication |
| spellingShingle | Anna Kobrzycka Paweł Napora Brandon L. Pearson Krystyna Pierzchała-Koziec Rafał Szewczyk Marek Wieczorek Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation Journal of Neuroinflammation Vagus nerve Vagotomy Prostaglandin E2 PGE2 Compensatory mechanisms CNS communication |
| title | Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation |
| title_full | Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation |
| title_fullStr | Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation |
| title_full_unstemmed | Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation |
| title_short | Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation |
| title_sort | peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation |
| topic | Vagus nerve Vagotomy Prostaglandin E2 PGE2 Compensatory mechanisms CNS communication |
| url | http://link.springer.com/article/10.1186/s12974-019-1544-y |
| work_keys_str_mv | AT annakobrzycka peripheralandcentralcompensatorymechanismsforimpairedvagusnervefunctionduringperipheralimmuneactivation AT pawełnapora peripheralandcentralcompensatorymechanismsforimpairedvagusnervefunctionduringperipheralimmuneactivation AT brandonlpearson peripheralandcentralcompensatorymechanismsforimpairedvagusnervefunctionduringperipheralimmuneactivation AT krystynapierzchałakoziec peripheralandcentralcompensatorymechanismsforimpairedvagusnervefunctionduringperipheralimmuneactivation AT rafałszewczyk peripheralandcentralcompensatorymechanismsforimpairedvagusnervefunctionduringperipheralimmuneactivation AT marekwieczorek peripheralandcentralcompensatorymechanismsforimpairedvagusnervefunctionduringperipheralimmuneactivation |