e16 Abstracts / Brain, Behavior, and Immunity 66 (2017) e1e42
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 todays 24/7 society
and has profound consequences on health and cognition. Recent evi-
dence indicates increased levels of inflammatory molecules follow-
ing 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 adap-
tor molecule-1 (Iba1)-immunoreactive (ir) microglia in brain regions
involved in sleep/wake and cognitive functions; microglia morphol-
ogy 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 double-
labeled 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
Ohio State University, Columbus, OH 43210, USA
Repeated subthreshold bacterial exposures in rodents cause
novel euflammation which attenuates neuroinflammation and sick-
ness 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 with-
out 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 cen-
tral inflammation in all mice, however neuroinflammation was less
attenuated in tumor-bearing mice compared with tumor-free
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 cau-
sally contributes to neuropathic pain. Investigation of neuroinflam-
matory pain mechanisms has focused on the peripheral and spinal
cord nociceptive pathways, whereas the brain has been largely unex-
plored. 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 affec-
tive components of pain. Chronic constriction injury (CCI) of the sci-
atic nerve was performed in male rats, and the spinal cords and
brains were collected either prior to surgery, 7 or 28 days post sur-
gery. 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 con-
trast, 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 dysreg-
ulate 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
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 Childrens Hosiptal, 700
Childrens 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 syn-
drome, 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