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The microglial response in a rat model of chronic sleep restriction
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Abstracts / Brain, Behavior, and Immunity 66 (2017) e1–e42
Abstract # 1929 The microglial response in a rat model of chronic sleep restriction S.E. Hall, S. Deurveilher, K. Semba Dalhousie University, Department of Medical Neuroscience, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada Chronic sleep restriction (CSR) is prevalent in today’s 24/7 society and has profound consequences on health and cognition. Recent evidence indicates increased levels of inflammatory molecules following CSR; however, the role of microglia, the resident immune cells of the brain, is unknown. Using a rat model of CSR (4 days) that we developed in our lab, we previously found that CSR initiated an increase in the number and density of ionized calcium binding adaptor molecule-1 (Iba1)-immunoreactive (ir) microglia in brain regions involved in sleep/wake and cognitive functions; microglia morphology was unaffected. Here, we explored the mechanisms underlying the region-specific increases in microglia numbers after CSR. First, proliferating cells were immunohistochemically identified using bromodeoxyuridine (BrdU). We found that the number of doublelabeled Iba1/BrdU-ir cells was not affected by CSR. Second, blood brain barrier permeability, assessed by examining extravasation of the fluorescent tracers sodium fluorescein and Evans blue into the brain tissue, was also unaffected by CSR. These results suggest that neither microglia proliferation nor the recruitment of peripheral macrophages across the blood-brain barrier contributed to the observed increase in Iba1-ir microglia after CSR, suggesting that increased Iba1 expression may be responsible for the effect. Preliminary results with qPCR indicate decreased mRNA expression (60%) of the pro-inflammatory interleukin-1b and tumor necrosis factor-a and increased expression (25%) of the anti-inflammatory IL-10 in the hippocampus after CSR. http://dx.doi.org/10.1016/j.bbi.2017.07.066
Abstract # 1930 Euflammation attenuates central and peripheral inflammation and cognitive consequences of an immune challenge after tumor development M. Pyter, S.R. Bever, X. Liu, N. Quan
controls. LPS-induced lethargy and cognitive impairments were more pronounced among tumor-bearing mice and were effectively attenuated with euflammation. Cognitive changes were independent of brain-derived growth factor gene expression in the hippocampus. These results suggest that induction of euflammation may alleviate the negative side effects of bacterial-based tumor treatments and attenuate behavioral comorbidities associated with cancer or other chronic diseases. http://dx.doi.org/10.1016/j.bbi.2017.07.067
Abstract # 1931 Mapping microglial reactivity in the brain after sciatic nerve injury M.J. Lacagnina, T.J. Fabisiak, P.M. Grace University of Texas MD Anderson Cancer Center, Critical Care Research, Unit 110, 1515 Holcombe Blvd, Houston, TX 77030, USA Injury to peripheral nerves induces neuroinflammation that causally contributes to neuropathic pain. Investigation of neuroinflammatory pain mechanisms has focused on the peripheral and spinal cord nociceptive pathways, whereas the brain has been largely unexplored. However, the brain is ultimately where the sensory and affective components of pain are encoded by a network of brain nuclei known as the ‘‘pain matrix”. The purpose of our study was to identify the extent to which peripheral nerve injury induces microglia activation in brain regions encoding the sensory and affective components of pain. Chronic constriction injury (CCI) of the sciatic nerve was performed in male rats, and the spinal cords and brains were collected either prior to surgery, 7 or 28 days post surgery. The fixed tissues were stained for CD11b. We found that CD11b expression was transient in structures encoding the sensory aspects of pain (e.g. somatosensory cortex, insular cortex). In contrast, CD11b expression was persistent in the nuclei that mediate affective pain components (e.g. central amygdala, anterior cingulate cortex, medial prefrontal cortex). Based on the known function of microglia, these data suggest that microglia may persistently dysregulate networks encoding negative affect after peripheral nerve injury, which will be tested in future studies. http://dx.doi.org/10.1016/j.bbi.2017.07.068
Ohio State University, Columbus, OH 43210, USA Repeated subthreshold bacterial exposures in rodents cause novel euflammation which attenuates neuroinflammation and sickness behaviors upon subsequent infectious challenges to the host. An advantage of this euflammation protocol is that it does not elicit illness behavior. Bacterial antitumor treatments are successful, but suboptimal due to their illness side effects. In addition, behavioral consequences (depression, cognitive impairments) to homeostatic challenges that are associated with inflammation are prevalent and reduce quality of life in cancer survivors. This study tested the potential for euflammation to attenuate behavioral consequences of an immune challenge in tumor-bearing mice. Mice with and without oral tumors in their flank received the established peripheral euflammatory protocol or vehicle, followed by an acute peripheral immune challenge (lipopolysaccharide [LPS] injection) or saline. Cognitive function and sickness behavior was assessed after the challenge and peripheral and central inflammatory responses were measured. Euflammation reduced LPS-induced peripheral and central inflammation in all mice, however neuroinflammation was less attenuated in tumor-bearing mice compared with tumor-free
Abstract # 1932 The colonic epithelial transcriptome and intestinal microbiome are significantly changed by social stressor exposure A.R. Mackos a, P. White a, M.T. Bailey a,b a The Research Institute at Nationwide Children’s Hosiptal, 700 Children’s Drive, Columbus, OH 43205, USA b The Ohio State University Wexner Medical Center, USA
Exposure to life stressors exacerbates gastrointestinal conditions, including inflammatory bowel diseases and irritable bowel syndrome, however the mechanisms by which this occurs have remained elusive. It is known that stressor exposure significantly alters the intestinal microbiota, which leads to dysregulated colonic inflammatory responses upon pathogen challenge. The link between stressor-induced microbial changes and the resulting enhanced immune response is not known, but colonic epithelial cells (CECs) are thought to be involved. We determined whether stressor
Abstracts / Brain, Behavior, and Immunity 66 (2017) e1–e42
Abstract # 1929 The microglial response in a rat model of chronic sleep restriction S.E. Hall, S. Deurveilher, K. Semba Dalhousie University, Department of Medical Neuroscience, Sir Charles Tupper Medical Building, 5850 College Street, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada Chronic sleep restriction (CSR) is prevalent in today’s 24/7 society and has profound consequences on health and cognition. Recent evidence indicates increased levels of inflammatory molecules following CSR; however, the role of microglia, the resident immune cells of the brain, is unknown. Using a rat model of CSR (4 days) that we developed in our lab, we previously found that CSR initiated an increase in the number and density of ionized calcium binding adaptor molecule-1 (Iba1)-immunoreactive (ir) microglia in brain regions involved in sleep/wake and cognitive functions; microglia morphology was unaffected. Here, we explored the mechanisms underlying the region-specific increases in microglia numbers after CSR. First, proliferating cells were immunohistochemically identified using bromodeoxyuridine (BrdU). We found that the number of doublelabeled Iba1/BrdU-ir cells was not affected by CSR. Second, blood brain barrier permeability, assessed by examining extravasation of the fluorescent tracers sodium fluorescein and Evans blue into the brain tissue, was also unaffected by CSR. These results suggest that neither microglia proliferation nor the recruitment of peripheral macrophages across the blood-brain barrier contributed to the observed increase in Iba1-ir microglia after CSR, suggesting that increased Iba1 expression may be responsible for the effect. Preliminary results with qPCR indicate decreased mRNA expression (60%) of the pro-inflammatory interleukin-1b and tumor necrosis factor-a and increased expression (25%) of the anti-inflammatory IL-10 in the hippocampus after CSR. http://dx.doi.org/10.1016/j.bbi.2017.07.066
Abstract # 1930 Euflammation attenuates central and peripheral inflammation and cognitive consequences of an immune challenge after tumor development M. Pyter, S.R. Bever, X. Liu, N. Quan
controls. LPS-induced lethargy and cognitive impairments were more pronounced among tumor-bearing mice and were effectively attenuated with euflammation. Cognitive changes were independent of brain-derived growth factor gene expression in the hippocampus. These results suggest that induction of euflammation may alleviate the negative side effects of bacterial-based tumor treatments and attenuate behavioral comorbidities associated with cancer or other chronic diseases. http://dx.doi.org/10.1016/j.bbi.2017.07.067
Abstract # 1931 Mapping microglial reactivity in the brain after sciatic nerve injury M.J. Lacagnina, T.J. Fabisiak, P.M. Grace University of Texas MD Anderson Cancer Center, Critical Care Research, Unit 110, 1515 Holcombe Blvd, Houston, TX 77030, USA Injury to peripheral nerves induces neuroinflammation that causally contributes to neuropathic pain. Investigation of neuroinflammatory pain mechanisms has focused on the peripheral and spinal cord nociceptive pathways, whereas the brain has been largely unexplored. However, the brain is ultimately where the sensory and affective components of pain are encoded by a network of brain nuclei known as the ‘‘pain matrix”. The purpose of our study was to identify the extent to which peripheral nerve injury induces microglia activation in brain regions encoding the sensory and affective components of pain. Chronic constriction injury (CCI) of the sciatic nerve was performed in male rats, and the spinal cords and brains were collected either prior to surgery, 7 or 28 days post surgery. The fixed tissues were stained for CD11b. We found that CD11b expression was transient in structures encoding the sensory aspects of pain (e.g. somatosensory cortex, insular cortex). In contrast, CD11b expression was persistent in the nuclei that mediate affective pain components (e.g. central amygdala, anterior cingulate cortex, medial prefrontal cortex). Based on the known function of microglia, these data suggest that microglia may persistently dysregulate networks encoding negative affect after peripheral nerve injury, which will be tested in future studies. http://dx.doi.org/10.1016/j.bbi.2017.07.068
Ohio State University, Columbus, OH 43210, USA Repeated subthreshold bacterial exposures in rodents cause novel euflammation which attenuates neuroinflammation and sickness behaviors upon subsequent infectious challenges to the host. An advantage of this euflammation protocol is that it does not elicit illness behavior. Bacterial antitumor treatments are successful, but suboptimal due to their illness side effects. In addition, behavioral consequences (depression, cognitive impairments) to homeostatic challenges that are associated with inflammation are prevalent and reduce quality of life in cancer survivors. This study tested the potential for euflammation to attenuate behavioral consequences of an immune challenge in tumor-bearing mice. Mice with and without oral tumors in their flank received the established peripheral euflammatory protocol or vehicle, followed by an acute peripheral immune challenge (lipopolysaccharide [LPS] injection) or saline. Cognitive function and sickness behavior was assessed after the challenge and peripheral and central inflammatory responses were measured. Euflammation reduced LPS-induced peripheral and central inflammation in all mice, however neuroinflammation was less attenuated in tumor-bearing mice compared with tumor-free
Abstract # 1932 The colonic epithelial transcriptome and intestinal microbiome are significantly changed by social stressor exposure A.R. Mackos a, P. White a, M.T. Bailey a,b a The Research Institute at Nationwide Children’s Hosiptal, 700 Children’s Drive, Columbus, OH 43205, USA b The Ohio State University Wexner Medical Center, USA
Exposure to life stressors exacerbates gastrointestinal conditions, including inflammatory bowel diseases and irritable bowel syndrome, however the mechanisms by which this occurs have remained elusive. It is known that stressor exposure significantly alters the intestinal microbiota, which leads to dysregulated colonic inflammatory responses upon pathogen challenge. The link between stressor-induced microbial changes and the resulting enhanced immune response is not known, but colonic epithelial cells (CECs) are thought to be involved. We determined whether stressor