Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior
| Autor: | A. de Vries, Graham A. W. Rook, Andrea Evans, Jacob Harvey Hollis, Jon R. F. Hunt, Julian F. R. Paton, E. van Kampen, B. Pan, Christopher A. Lowry, Stafford L. Lightman, DM Knight, Laura Rosa Brunet |
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| Jazyk: | angličtina |
| Předmět: |
Male
Time Factors hippocampus Emotions 5-HT Stimulation S.E.M. standard error of the mean vagus SolDL dorsolateral part of the nucleus of the solitary tract TNF-α tumor necrosis factor-α Mice 0302 clinical medicine Neural Pathways Limbic System IL-6 interleukin-6 Sickness behavior ANOVA analysis of variance 5-HT serotonin Cerebral Cortex Neurons 0303 health sciences Mice Inbred BALB C prefrontal cortex Behavior Animal General Neuroscience Drug Administration Routes mlf medial longitudinal fasciculus IL-10 interleukin-10 c-Fos-ir c-Fos-like-immunoreactive Bacterial vaccine AP area postrema Treg T regulatory cell OVA-NC ovalbumin coupled to nitrocellulose beads Bacterial Vaccines depression DR dorsal raphe nucleus LSD least significant difference Mv-NC Mycobacterium vaccae antigen M. vaccae coupled to nitrocellulose beads LPS lipopolysaccharide Cytokines Psychology nTS nucleus of the solitary tract PBST phosphate-buffered saline containing 0.3% Triton X-100 Serotonin Neuroscience(all) PBS phosphate-buffered saline Serotonergic ROb raphe obscurus HPLC high pressure liquid chromatography 03 medical and health sciences DRI dorsal raphe nucleus interfascicular part OVA ovalbumin Immune system TGF-β transforming growth factor-β raphe Animals NC nitrocellulose beads Bronchopulmonary Sequestration Th1 T helper cell 1 030304 developmental biology 5-HIAA 5-hydroxyindoleacetic acid PBG phenylbiguanide Brain Chemistry Analysis of Variance Raphe EDTA ethylenediaminetetraacetic acid RMg raphe magnus i.t. intratracheal Th2 T helper cell 2 Neuroanatomy EMG electromyogram Disease Models Animal Anxiogenic M. vaccae Mycobacterium vaccae DRC dorsal raphe nucleus caudal part Raphe Nuclei ECG electrocardiogram Raphe nuclei Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2007.01.067 |
| Popis: | Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes. |
| Databáze: | OpenAIRE |
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