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Abstract # 2061 Brief stress management interventions after surgery improve psychological adaptation and immune cell signaling in breast cancer patients
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Abstracts / Brain, Behavior, and Immunity 76 (2019) e1–e43
of GFAP in the hippocampus of rats that received a hypercaloric or a normocaloric diet for 60 days. Adult male Wistar rats received a cafeteria diet with food items chosen to reflect the enormous variety, palatability and energy density of the modern western diet. They included standard rodent chow (37.5%), peanut (12.5%), corn starch biscuit (12.5%), condensed milk (12.5%), and chocolate (25%), providing an average of 4.2 kcal/g, 38% fat, 14% protein and 48% carbohydrate. Some rats received only standard commercial rodent chow, providing 2.8 kcal/g, 13% fat, 32% protein and 55% carbohydrate. Body weight of the animals was measured twice per week. After 60 days, brains were collected for GFAP immunohistochemical investigation in the hippocampus and hypothalamus. Astrocytic reactivity was assessed by morphometry. Results showed that the cafeteria diet induced obese animals, which presented an increased GFAP expression in both areas. This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese animals. http://dx.doi.org/10.1016/j.bbi.2018.11.187
Abstract # 2060 Microglia are extrinsically primed by the aged microenvironment S.M. O’Neil, K.G. Witcher, J.P. Godbout The Ohio State University, 247 IBMR Building, 460 Medical Center Drive, Columbus, OH 43210, United States Microglia are responsible for propagating inflammatory signals from the periphery to the brain, where they drive the behavioral sickness response. With normal aging, these cells develop a proinflammatory, ‘‘primed” profile with increased expression of inflammatory mediators. A critical question is if this priming can be reversed. CSF1R antagonism results in elimination of microglia in the adult brain followed by rapid repopulation. Therefore, we hypothesized CSF1R antagonist-mediated microglial depletion in the aged brain would result in repopulation of new, unprimed microglia. Here we provide evidence that microglia in adult and aged mice were robustly eliminated following oral administration of CSF1R antagonist PLX5622. When antagonism was stopped, microglia repopulated the adult and aged brain at the same rate and efficiency with new cells no longer burdened with lipofuscin, the hallmark lipid debris of aging. However, RNA-Seq analysis of FACSsorted microglia revealed these new microglia had the same primed mRNA profile. Moreover, RNA-Seq analysis of the brain microenvironment provided evidence of astrogliosis in aged mice independent of microglial depletion/repopulation. Lastly, peripheral immune challenge still caused an exaggerated microglial inflammatory response in the aged brain with prolonged behavioral deficits. These data are interpreted to indicate the microenvironment of the aged brain significantly influences the profile of repopulating/proliferating microglia. Taken together, aged microglia proliferate and repopulate the CNS, but the repopulating microglia still adopt a pro-inflammatory profile characteristic of aging. http://dx.doi.org/10.1016/j.bbi.2018.11.188
Abstract # 2061 Brief stress management interventions after surgery improve psychological adaptation and immune cell signaling in breast cancer patients M.H. Antoni a,b, A. Diaz a, C. Taub a, H. Fisher a, C.S. Carver a, M. Lippman a,b, B. Hudson a,b, B.B. Blomberg a,b
a Dept of Psychology, Dept of Microbiology/Immunology, University of Miami School of Medicine, Coral Gables, FL 33124, United States b Sylvester Comprehensive Cancer Center, United States
Introduction: Breast cancer (BCa) patients revealing poorer psychological adaptation after surgery show greater inflammation and have poorer long-term outcomes. Our 10-wk group cognitive behavioral stress management (CBSM) intervention showed concomitant 12-month improvements in adaptation and downregulated leukocyte pro-inflammatory and pro-metastatic and upregulated glucocorticoid (GC) regulatory and anti-viral gene expression vs psychoeducation controls. Methods: In a dismantling trial (N = 183) we compared 5-wk postsurgical interventions featuring one CBSM component—Cognitive Behavioral Therapy [CBT] or Relaxation Training [RT]—vs a 5-wk Health Education (HE) control for effects on adaptation and inflammatory signaling over 12 months of BCa treatment. Since bioinformatics analysis of the 10-wk CBSM trial inferred reduced NFjB signaling underlying CBSM effects on downstream leukocyte gene expression, we extracted nuclear protein from PBMCs to determine NFjB DNA binding by electromobility shift assay. Results: Women assigned to CBT or RT showed improved adaptation (affect and social disruption) and decreased NFjB binding over 12-months vs HE (p’s <.05). Greater adaptation at 12-months was associated with less NFjB-DNA binding. RT or CBT also showed reductions (vs HE) in ligands (s100A8/A9) for the Receptor for Advanced Glycation End Products (RAGE), which is implicated in NFjB activation and MAPK-mediated pro-metastatic processes (p < .05). Conclusion: Providing post-surgical BCa patients with brief stress management can improve adaptation and immune cell signaling during primary treatment, and may improve long-term health outcomes. http://dx.doi.org/10.1016/j.bbi.2018.11.189
Abstract # 2062 Affective status and immune responses to influenza vaccine in older persons living in South Florida M.H. Antoni a,b, A. Diaz a, M. Romero a, D. Frasca a, B.B. Blomberg a,b a Dept of Microbiology/Immunology, University of Miami School of Medicine, Psychology, 5665 Ponce DeLeon Blvd, Coral Gables, FL 33124, United States b Sylvester Comprehensive Cancer Center, United States
Background: Psychosocial factors predict poor influenza vaccine (IV) response. Aging and negative affect (NA) may dampen IV response by reducing class switch recombination (CSR), a B-cell process primed by IV. We examined whether greater positive affect [PA] and less NA pre- and post-IV relates to greater antibody responses and CSR in older persons receiving IV. Method: Older healthy persons (>60 yrs) completed the Affect Balance Scale (ABS) for NA and PA pre and post-IV in two separate Flu seasons. They received trivalent IV (H1N1, H3N2, B), and were re-assessed at 7 (t7)and 28 days (t28) for HAI titers and % switched B-cells (IgG+/IgA+CD27+) to quantify CSR. Results: Season 1: greater PA was associated with greater HAI titer Fold increase and greater CSR at t28. NA at t28 correlated with less CSR (p’s <.05). Season 2: greater PA related to greater overall HAI titer fold increase at t28; greater H1N1 titers at t7 and t28; greater H3N2 titers at t28; greater B-titers at t7 and t28. NA was associated with lower HAI titer fold increase by t28, and lower H3N2 titers at t7 and t28. Greater pre-vaccine PA predicted a larger HAI fold increase
Abstracts / Brain, Behavior, and Immunity 76 (2019) e1–e43
of GFAP in the hippocampus of rats that received a hypercaloric or a normocaloric diet for 60 days. Adult male Wistar rats received a cafeteria diet with food items chosen to reflect the enormous variety, palatability and energy density of the modern western diet. They included standard rodent chow (37.5%), peanut (12.5%), corn starch biscuit (12.5%), condensed milk (12.5%), and chocolate (25%), providing an average of 4.2 kcal/g, 38% fat, 14% protein and 48% carbohydrate. Some rats received only standard commercial rodent chow, providing 2.8 kcal/g, 13% fat, 32% protein and 55% carbohydrate. Body weight of the animals was measured twice per week. After 60 days, brains were collected for GFAP immunohistochemical investigation in the hippocampus and hypothalamus. Astrocytic reactivity was assessed by morphometry. Results showed that the cafeteria diet induced obese animals, which presented an increased GFAP expression in both areas. This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese animals. http://dx.doi.org/10.1016/j.bbi.2018.11.187
Abstract # 2060 Microglia are extrinsically primed by the aged microenvironment S.M. O’Neil, K.G. Witcher, J.P. Godbout The Ohio State University, 247 IBMR Building, 460 Medical Center Drive, Columbus, OH 43210, United States Microglia are responsible for propagating inflammatory signals from the periphery to the brain, where they drive the behavioral sickness response. With normal aging, these cells develop a proinflammatory, ‘‘primed” profile with increased expression of inflammatory mediators. A critical question is if this priming can be reversed. CSF1R antagonism results in elimination of microglia in the adult brain followed by rapid repopulation. Therefore, we hypothesized CSF1R antagonist-mediated microglial depletion in the aged brain would result in repopulation of new, unprimed microglia. Here we provide evidence that microglia in adult and aged mice were robustly eliminated following oral administration of CSF1R antagonist PLX5622. When antagonism was stopped, microglia repopulated the adult and aged brain at the same rate and efficiency with new cells no longer burdened with lipofuscin, the hallmark lipid debris of aging. However, RNA-Seq analysis of FACSsorted microglia revealed these new microglia had the same primed mRNA profile. Moreover, RNA-Seq analysis of the brain microenvironment provided evidence of astrogliosis in aged mice independent of microglial depletion/repopulation. Lastly, peripheral immune challenge still caused an exaggerated microglial inflammatory response in the aged brain with prolonged behavioral deficits. These data are interpreted to indicate the microenvironment of the aged brain significantly influences the profile of repopulating/proliferating microglia. Taken together, aged microglia proliferate and repopulate the CNS, but the repopulating microglia still adopt a pro-inflammatory profile characteristic of aging. http://dx.doi.org/10.1016/j.bbi.2018.11.188
Abstract # 2061 Brief stress management interventions after surgery improve psychological adaptation and immune cell signaling in breast cancer patients M.H. Antoni a,b, A. Diaz a, C. Taub a, H. Fisher a, C.S. Carver a, M. Lippman a,b, B. Hudson a,b, B.B. Blomberg a,b
a Dept of Psychology, Dept of Microbiology/Immunology, University of Miami School of Medicine, Coral Gables, FL 33124, United States b Sylvester Comprehensive Cancer Center, United States
Introduction: Breast cancer (BCa) patients revealing poorer psychological adaptation after surgery show greater inflammation and have poorer long-term outcomes. Our 10-wk group cognitive behavioral stress management (CBSM) intervention showed concomitant 12-month improvements in adaptation and downregulated leukocyte pro-inflammatory and pro-metastatic and upregulated glucocorticoid (GC) regulatory and anti-viral gene expression vs psychoeducation controls. Methods: In a dismantling trial (N = 183) we compared 5-wk postsurgical interventions featuring one CBSM component—Cognitive Behavioral Therapy [CBT] or Relaxation Training [RT]—vs a 5-wk Health Education (HE) control for effects on adaptation and inflammatory signaling over 12 months of BCa treatment. Since bioinformatics analysis of the 10-wk CBSM trial inferred reduced NFjB signaling underlying CBSM effects on downstream leukocyte gene expression, we extracted nuclear protein from PBMCs to determine NFjB DNA binding by electromobility shift assay. Results: Women assigned to CBT or RT showed improved adaptation (affect and social disruption) and decreased NFjB binding over 12-months vs HE (p’s <.05). Greater adaptation at 12-months was associated with less NFjB-DNA binding. RT or CBT also showed reductions (vs HE) in ligands (s100A8/A9) for the Receptor for Advanced Glycation End Products (RAGE), which is implicated in NFjB activation and MAPK-mediated pro-metastatic processes (p < .05). Conclusion: Providing post-surgical BCa patients with brief stress management can improve adaptation and immune cell signaling during primary treatment, and may improve long-term health outcomes. http://dx.doi.org/10.1016/j.bbi.2018.11.189
Abstract # 2062 Affective status and immune responses to influenza vaccine in older persons living in South Florida M.H. Antoni a,b, A. Diaz a, M. Romero a, D. Frasca a, B.B. Blomberg a,b a Dept of Microbiology/Immunology, University of Miami School of Medicine, Psychology, 5665 Ponce DeLeon Blvd, Coral Gables, FL 33124, United States b Sylvester Comprehensive Cancer Center, United States
Background: Psychosocial factors predict poor influenza vaccine (IV) response. Aging and negative affect (NA) may dampen IV response by reducing class switch recombination (CSR), a B-cell process primed by IV. We examined whether greater positive affect [PA] and less NA pre- and post-IV relates to greater antibody responses and CSR in older persons receiving IV. Method: Older healthy persons (>60 yrs) completed the Affect Balance Scale (ABS) for NA and PA pre and post-IV in two separate Flu seasons. They received trivalent IV (H1N1, H3N2, B), and were re-assessed at 7 (t7)and 28 days (t28) for HAI titers and % switched B-cells (IgG+/IgA+CD27+) to quantify CSR. Results: Season 1: greater PA was associated with greater HAI titer Fold increase and greater CSR at t28. NA at t28 correlated with less CSR (p’s <.05). Season 2: greater PA related to greater overall HAI titer fold increase at t28; greater H1N1 titers at t7 and t28; greater H3N2 titers at t28; greater B-titers at t7 and t28. NA was associated with lower HAI titer fold increase by t28, and lower H3N2 titers at t7 and t28. Greater pre-vaccine PA predicted a larger HAI fold increase