- Email: [email protected]
22. Galectin-9 is increased during cuprizone intoxication and promotes remyelination
Abstracts from the 21st Annual PNIRS Meeting 40 (2014) e1–e52 d Department of Periodontics, University of Illinois at Chicago, Chicago, IL, USA e Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, IL, USA f College of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
In separate past studies, higher inflammatory responses have been associated with the pathogenesis of periodontal disease (Periodontitis) and delayed wound healing in oral mucosa. The relationship between these factors is yet to be investigated. Using a standardized model of wound healing, this study objectively examined differences in oral mucosal healing rates and local tissue inflammation in response to wounding between individuals with Periodontitis and healthy controls. This study involved 20 systemically healthy, non-smoking, adult male participants (24–45 years); 10 individuals with untreated periodontitis and 10 healthy agematched controls. Three excisional wounds were placed on the hard palate under local anesthesia, and were standardized for size, location, depth, and time of placement. Oral mucosal healing rates were determined using daily videographs. Tissue was biopsied at 0 h, 6 h and 24 h post-wounding and analyzed for inflammation using realtime PCR. It was found that wound healing in systemically healthy young men with periodontitis is the same as healing in men without periodontitis in an unaffected area of the mouth. Local tissue inflammation at baseline and after wounding (6 h and 24 h) also did not differ between groups. This suggests that periodontal disease and its associated inflammation, even when untreated, does not affect healing in unaffected oral tissues. These results have direct clinical implications on the timing and management of surgical procedures in patients with untreated Periodontitis. http://dx.doi.org/10.1016/j.bbi.2014.06.041
22. Galectin-9 is increased during cuprizone intoxication and promotes remyelination A.J. Steelman, J. Li Texas A&M University, College of Veterinary Medicine, Department of Veterinary Integrative Biosciences, College Station, TX 77843-4458, USA Demyelination and axonal damage in multiple sclerosis (MS) results from inflammatory processes that are perpetuated by activated glia and infiltrating leukocytes. Galectins are beta-galactoside binding lectins, capable of modulating immune responses. The function of galectin-9 (Gal-9) upregulation in MS is important since it has been reported to promote innate immune responses while at the same time inhibit autoimmunity. Cuprizone intoxication causes reproducible demyelination of the caudal corpus callosum that is associated with reactive gliosis. Removal of cuprizone from the diet results in remyelination. Using wild-type (WT) and galectin-9 null (Lgals9 / ) mice we investigated the effects Gal-9 on the pathogenesis of this model of MS. Gal-9 was increased in the corpus callosum during cuprizone intoxication where it localized to both GFAP+ astrocytes and Iba-1+ microglia. However, the degree of demyelination and reactive gliosis were similar between genotypes. Likewise, reactive gliosis did not differ between WT and Lgals9 / mice during a time-frame corresponding to remyelination. In contrast, WT mice displayed enhance remyelination when compared to Lgals9 / mice as determined by oil Red O staining for myelin. Interestingly, Lgals9 / mice had significantly fewer mature oligodendrocytes (OLs) (CC1+) than their WT counterparts while the numbers of total OLs (Olig2+) did not differ between genotype. Finally, treatment of mixed glial cultures with recombinant Gal-9 promoted OL
e7
maturation. Together these data indicate galectin-9 promotes oligodendrocyte maturation remyelination. http://dx.doi.org/10.1016/j.bbi.2014.06.042
23. Allostatic associations in women veterans with histories of childhood sexual assault M.E. Groer, E. Kostas-Polston, C. Dillahunt-Aspilliga, V. Johnson-Mallard, A.R. Duffy University of South Florida, College of Nursing, 12910 Bruce B. Downs Blvd., Tampa, FL 33612, USA Women veterans have increased sexual victimization before entering the military and increased military sexual trauma (MST). Using the allostatic load model, we studied relationships between hair cortisol, cardiovascular and inflammatory biomarkers, stress, pain, PTSD, and history and frequency of childhood rape or attempted rape in 81 women veterans. The latter was reported by 27 women (33%). There was a trend for lower hair cortisol in these women [t(63.92) = 1.91, p = .06], suggesting a dampened hypothalamic–hypophyseal–pituitary axis. These women also had higher cholesterol [t(69) = 2.62, p = .01] and triglycerides [t(68) = 2.23, p = .03], higher perceived stress scores [t(77) = 2.00, p = .05], greater pain [t(78) = 3.32, p = .01], greater fatigue [t(77) = 2.03, p = .05], and there was a trend for lower plasma IL10 [t(56.75) = 1.87, p = .07] than women veterans without this history. We did not find evidence of higher CRP or IL-6 as has been reported in other studies, but many of these women were on medications that could suppress inflammation (antidepressants, anxiolytics, anti-hypertenives, statins, and anti-inflammatories). Of the 27 women who reported childhood sexual assault, 10 (37%) also reported MST. These data suggest that some women veterans who have suffered childhood sexual assault are vulnerable and have increased allostatic load and propensity for a variety of later illnesses. http://dx.doi.org/10.1016/j.bbi.2014.06.043
24. Tumor progression increases neuroinflammation, fatigue and depressive-like behavior without altering muscle function D.M. Norden a, S. Bicer b, R. Jing c, C.J. Henry a, L.E. Wold c, P.J. Reiser b, D.O. McCarthy c, J.P. Godbout a,d a
Department of Neuroscience, The Ohio State University, 333 W. 10th Ave, Columbus, OH 43210, USA b Department of Oral Biology, USA c College of Nursing, USA d Institute for Behavioral Medicine Research, USA Cancer patients frequently suffer concomitantly from loss of muscle mass, fatigue and depression. Understanding cancer-related fatigue (CRF) is critical because it negatively influences quality of life, functional independence, and survival. In the present study, we used a mouse model of tumor progression to discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor progression over time was associated with increased fatigue, reduced body and muscle mass, and increased depressive-like behavior. Tumor induced fatigue, however, was independent of the functional capabilities of skeletal muscle. Moreover, fatigue, depressive-like behavior and increased cytokine expression in the brain were evident in tumor bearing mice within the first 2 weeks and preceded the loss of body and muscle mass. For example, within 2 weeks of tumor progression there was reduced voluntary wheel running activity and
In separate past studies, higher inflammatory responses have been associated with the pathogenesis of periodontal disease (Periodontitis) and delayed wound healing in oral mucosa. The relationship between these factors is yet to be investigated. Using a standardized model of wound healing, this study objectively examined differences in oral mucosal healing rates and local tissue inflammation in response to wounding between individuals with Periodontitis and healthy controls. This study involved 20 systemically healthy, non-smoking, adult male participants (24–45 years); 10 individuals with untreated periodontitis and 10 healthy agematched controls. Three excisional wounds were placed on the hard palate under local anesthesia, and were standardized for size, location, depth, and time of placement. Oral mucosal healing rates were determined using daily videographs. Tissue was biopsied at 0 h, 6 h and 24 h post-wounding and analyzed for inflammation using realtime PCR. It was found that wound healing in systemically healthy young men with periodontitis is the same as healing in men without periodontitis in an unaffected area of the mouth. Local tissue inflammation at baseline and after wounding (6 h and 24 h) also did not differ between groups. This suggests that periodontal disease and its associated inflammation, even when untreated, does not affect healing in unaffected oral tissues. These results have direct clinical implications on the timing and management of surgical procedures in patients with untreated Periodontitis. http://dx.doi.org/10.1016/j.bbi.2014.06.041
22. Galectin-9 is increased during cuprizone intoxication and promotes remyelination A.J. Steelman, J. Li Texas A&M University, College of Veterinary Medicine, Department of Veterinary Integrative Biosciences, College Station, TX 77843-4458, USA Demyelination and axonal damage in multiple sclerosis (MS) results from inflammatory processes that are perpetuated by activated glia and infiltrating leukocytes. Galectins are beta-galactoside binding lectins, capable of modulating immune responses. The function of galectin-9 (Gal-9) upregulation in MS is important since it has been reported to promote innate immune responses while at the same time inhibit autoimmunity. Cuprizone intoxication causes reproducible demyelination of the caudal corpus callosum that is associated with reactive gliosis. Removal of cuprizone from the diet results in remyelination. Using wild-type (WT) and galectin-9 null (Lgals9 / ) mice we investigated the effects Gal-9 on the pathogenesis of this model of MS. Gal-9 was increased in the corpus callosum during cuprizone intoxication where it localized to both GFAP+ astrocytes and Iba-1+ microglia. However, the degree of demyelination and reactive gliosis were similar between genotypes. Likewise, reactive gliosis did not differ between WT and Lgals9 / mice during a time-frame corresponding to remyelination. In contrast, WT mice displayed enhance remyelination when compared to Lgals9 / mice as determined by oil Red O staining for myelin. Interestingly, Lgals9 / mice had significantly fewer mature oligodendrocytes (OLs) (CC1+) than their WT counterparts while the numbers of total OLs (Olig2+) did not differ between genotype. Finally, treatment of mixed glial cultures with recombinant Gal-9 promoted OL
e7
maturation. Together these data indicate galectin-9 promotes oligodendrocyte maturation remyelination. http://dx.doi.org/10.1016/j.bbi.2014.06.042
23. Allostatic associations in women veterans with histories of childhood sexual assault M.E. Groer, E. Kostas-Polston, C. Dillahunt-Aspilliga, V. Johnson-Mallard, A.R. Duffy University of South Florida, College of Nursing, 12910 Bruce B. Downs Blvd., Tampa, FL 33612, USA Women veterans have increased sexual victimization before entering the military and increased military sexual trauma (MST). Using the allostatic load model, we studied relationships between hair cortisol, cardiovascular and inflammatory biomarkers, stress, pain, PTSD, and history and frequency of childhood rape or attempted rape in 81 women veterans. The latter was reported by 27 women (33%). There was a trend for lower hair cortisol in these women [t(63.92) = 1.91, p = .06], suggesting a dampened hypothalamic–hypophyseal–pituitary axis. These women also had higher cholesterol [t(69) = 2.62, p = .01] and triglycerides [t(68) = 2.23, p = .03], higher perceived stress scores [t(77) = 2.00, p = .05], greater pain [t(78) = 3.32, p = .01], greater fatigue [t(77) = 2.03, p = .05], and there was a trend for lower plasma IL10 [t(56.75) = 1.87, p = .07] than women veterans without this history. We did not find evidence of higher CRP or IL-6 as has been reported in other studies, but many of these women were on medications that could suppress inflammation (antidepressants, anxiolytics, anti-hypertenives, statins, and anti-inflammatories). Of the 27 women who reported childhood sexual assault, 10 (37%) also reported MST. These data suggest that some women veterans who have suffered childhood sexual assault are vulnerable and have increased allostatic load and propensity for a variety of later illnesses. http://dx.doi.org/10.1016/j.bbi.2014.06.043
24. Tumor progression increases neuroinflammation, fatigue and depressive-like behavior without altering muscle function D.M. Norden a, S. Bicer b, R. Jing c, C.J. Henry a, L.E. Wold c, P.J. Reiser b, D.O. McCarthy c, J.P. Godbout a,d a
Department of Neuroscience, The Ohio State University, 333 W. 10th Ave, Columbus, OH 43210, USA b Department of Oral Biology, USA c College of Nursing, USA d Institute for Behavioral Medicine Research, USA Cancer patients frequently suffer concomitantly from loss of muscle mass, fatigue and depression. Understanding cancer-related fatigue (CRF) is critical because it negatively influences quality of life, functional independence, and survival. In the present study, we used a mouse model of tumor progression to discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor progression over time was associated with increased fatigue, reduced body and muscle mass, and increased depressive-like behavior. Tumor induced fatigue, however, was independent of the functional capabilities of skeletal muscle. Moreover, fatigue, depressive-like behavior and increased cytokine expression in the brain were evident in tumor bearing mice within the first 2 weeks and preceded the loss of body and muscle mass. For example, within 2 weeks of tumor progression there was reduced voluntary wheel running activity and