- Email: [email protected]
Age-related increase in microglia proliferation in the hippocampus
S210
PNIRS meeting abstracts / Brain, Behavior, and Immunity 25 (2011) S179–S242
107. Elevated salivary C-reactive protein in maltreated children A. Danese, I. Ouellet-Morin, L. Arseneault
gle dose of treatment in our model; we are currently investigating which mechanism is involved in such effect.
Institute of Psychiatry, King’s College London, 16 DeCrespigny Park, London, SE5 8AF, Great Britain and Northern Ireland, UK
doi:10.1016/j.bbi.2011.07.111
Background: Childhood maltreatment is linked to elevated inflammation levels in adult life. There is only initial evidence suggesting that these life-course effects emerge in childhood years. We aimed to expand previous evidence by measuring inflammation levels in maltreated children using a newly validated non-invasive assay for C-reactive protein (CRP) in saliva. Methods: Participants were recruited from the E-Risk Longitudinal Twin Study, which tracks the development of a nationally-representative birth cohort of 2232 British children. From the total E-Risk sample, we identified 190 12-year-old identical twins eligible to participate in a sub-study of stress biology. Maltreatment was prospectively assessed through validated interviews with mothers. Inflammation was measured through salivary CRP. Results: Analyses adjusted for sex, age, pubertal stage, and anti-inflammatory medication use showed that maltreated children exhibited elevated salivary CRP levels compared to non-maltreated children (p = .021). The elevated inflammation levels observed in maltreated children were not explained by BMI, socio-economic status, and depressive symptoms. Conclusion: Maltreated children show elevated inflammation levels already at age 12 years. Therefore, interventions to prevent the long-term effects of childhood maltreatment on adult mental and physical health should start in childhood. doi:10.1016/j.bbi.2011.07.110
108. Cannabidiol produces a long-term anti-inflammatory effect in a murine model of acute lung injury A. Ribeiro a, V. Ferraz-de-Paula a, M.L. Pinheiro a, W.M. Quinteiro-Filho a, A.T. Akamine a, V.I. Almeida a, A. Zager a, J.E. Hallak b, A.W. Zuardi b, J.A. Crippa b, J. Palermo-Neto a a School of Veterinary Medicine, University of Sao Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, Sao Paulo, Sao Paulo 05508-270, Brazil b Department of Neuroscience and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
Endocannabinoid system has become a topic of great interest in pharmacology. Therefore, we analyzed long-term effects of cannabidiol in a murine model of acute lung injury. C57BL/6 male mice were divided randomly in three groups, vehicle + PBS (veh + PBS), vehicle + LPS (veh + LPS) and cannabidiol + LPS CBD + LPS (CBD 20 mg/ kg). Mice were treated (i.p.) with vehicle or CBD and 60 min later received intranasal (i.n.) instillation of LPS or sterile PBS. One, two, four, and seven days later mice were killed by exsanguination and bronchoalveolar lavage fluid (BAL) was collected to measure total cell count and cytokine/chemokine production and lung was harvested to analyze leukocyte infiltration (hematoxylin/eosin staining). We observed that on day 1, 2 and 4 total cell count in the BAL was increased (p < .05) in the veh + LPS group and CBD prevented such increase by 50% (p < .05). We also observed that CBD modulates cytokine/chemokine production quantified in the BAL: on day 1 and 2 we observed that CBD treatment prevented MIP-2, TNF, and IL-6 increasing (p < .05); additionally, a tendency towards decreasing MCP-1 on day 1 and 2 (p = .1) and increasing IL-10 on day 2 (p = .1) was verified. Finally, we observed that CBD treatment prevented mainly neutrophil migration into the lungs. Thus, we show that CBD has a long-term anti-inflammatory effect with a sin-
109. Individual variation in inflammatory physiology: Modulation by serotonin W. Amaral a, G. Lubach a, A. Bennett b, C. Coe a a
The University of Wisconsin-Madison, Harlow Center for Biological Psychology, 22 N. Charter Street, Madison, WI 53715, USA b Wake Forest University Health Sciences, USA Our study used a nonhuman primate model to investigate whether a functional length polymorphism in the promoter of the serotonin transporter gene, 5-HTTLPR, helps to explain individual variation in proinflammatory immune responses. In the nervous system, the serotonin transporter regulates uptake of 5HT from the synaptic cleft following release and therefore affects serotonergic efficiency. The short 5-HTTLPR variant that acts as a dominant allele, is characterized by lower transcription rates, reduced uptake and increased extracellular 5HT, and has been associated with emotional reactivity and depression. Serotonin is also present in the gut and blood compartments, where it influences vessel permeability, cell trafficking, and inflammatory responses of leukocytes. Twenty juvenile male rhesus monkeys were genotyped and cytokine release characterized after overnight stimulation of blood cultures with LPS. The amount of IL-6 in the supernatant was also compared when the cells were pretreated with 5HT before adding LPS to the wells. A secondary goal was also to determine if a monkey’s genotype and inflammatory bias was associated with either its dominance status in the social groups comprised of 4–6 animals or its temperament, Our findings extend the significance of 5HT from its role as a neurotransmitter to its function as modulator of inflammation in the periphery, where high rather than low levels would be associated with greater emotionality. doi:10.1016/j.bbi.2011.07.112
110. Age-related increase in microglia proliferation in the hippocampus R.A. Kohman, E.K. DeYoung, J.S. Rhodes Department of Psychology, University of Illinois, Beckman Institute, Urbana, IL 61801, USA Aging is associated with neuroinflammation that may contribute to cognitive deficits and reductions in neural plasticity. The enhanced neuroinflammation is attributed to increased expression of inflammatory mediators by microglia, but increased proliferation may also contribute. Prior in vitro work indicates that aging increases microglia proliferation (Rozovsky et al., 1998). The current study evaluated the effects of aging on microglia proliferation within the hippocampus and whether exercise modulates the proliferation and/or activation state of microglia, as microglia can acquire an inflammatory or neuroprotective phenotype. We also assessed hippocampal neurogenesis to determine whether changes in microglia were associated with neuron survival. Adult (3.5 months) and aged (18 months) male BALB/c mice were individually housed with or without running wheels for 8 weeks. During the initial ten days, mice received Bromodeoxyuridine injections to label dividing cells.
PNIRS meeting abstracts / Brain, Behavior, and Immunity 25 (2011) S179–S242
Immunofluorescence was conducted to measure microglia proliferation, insulin-like growth factor (IGF) expression, and neuron survival. Expression of the trophic factor IGF was assessed as an indication of alternative activation. Results show that microglia proliferation was increased in aged mice, which exercise tended to reduce. Exercise enhanced survival of new neurons in both age groups. Though still in progress, we hypothesize a reduction in IGF expressing microglia in aged mice. Ultimately, findings will further our understanding of how exercise modulates neuroimmune activity and the potential influence on neural plasticity. doi:10.1016/j.bbi.2011.07.113
S211
post-wounding and assessed for inflammation via RT-PCR analysis of inflammation-related gene expression. Results: Exercise sped wound healing rate in obese mice compared to sedentary controls over the first 5 days post-wounding (p = .05). Although wound inflammation was not statistically different (p > .05), exercise resulted in an approximately 1.5 to 2.5-fold induction in the gene expression of F4/80, IL-10, TNF-alpha, CD206, and MCP-1 in the wound tissue at day 1 post-wounding. Conclusion: Contrary to our hypothesis, inflammation in exercise mice tended to be higher at 1 day postwounding. Additionally, markers of alternative activation of macrophages were upregulated. These data suggest a role for exercise in speeding the inflammatory process and altering the phenotype of inflammatory cells to one which promotes healing.
111. Stress, autonomic nervous system imbalance and psychopathology A. Halaris, E. Meresh, J. Fareed, S. Kimmons, J. Sinacore, N. Ruys
doi:10.1016/j.bbi.2011.07.115
Loyola University Stritch School of Medicine, Psychiatry, 2160 South First Avenue, Maywood, IL 60153, USA
113. Daily stressors and marital interactions affect diurnal cortisol and alpha-amylase rhythm in spouses of persons with mild cognitive impairment J.S. Savla, K.A. Roberto, R. Blieszner
Cardiovascular disease (CVD) and major depression (MDD) are two of the world’s leading health problems and they are highly interrelated. Repeated episodes of stress, anxiety, and depression can lead to a chronic pro-inflammatory status culminating in atherosclerosis and ultimately cardiovascular and cerebrovascular disease. Patients with MDD have higher levels of perceived stress compared to healthy controls. The harmful effects of chronic stress and depression on cardiovascular health have been documented for many years. Mental stress can result in a prolonged increase in aortic stiffness and can induce vascular stiffening even in young apparently healthy subjects with no traditional CVD risk factors. Psychological stress has been correlated with structural changes in arteries eventually leading to endothelial injury with atherothrombotic sequealae. Anxiety is a major risk factor for myocardial infarction (MI) and anxiety among initially healthy persons often predicts future acute MI or death due to cardiovascular disease, independent of other major risk factors. We conducted an open-label study comparing patients with MDD and matched healthy controls and sought to determine the level of stress perception before and after treatment with escitalopram. Additionally we assessed the degree of inflammation and arterial stiffness present in our subjects at pretreatment and whether the depressed patients showed normalization of inflammation biomarkers and arterial stiffness following successful treatment with escitalopram. doi:10.1016/j.bbi.2011.07.114
112. Effects of exercise on wound healing and wound tissue inflammation in obese mice B.D. Pence, S.A. Martin, J.A. Woods University of Illinois at Urbana-Champaign, 906 S Goodwin Ave, Urbana, IL 61801, USA Introduction: Impaired wound healing remains a major health concern for obese individuals. Studies show that prolonged inflammation in the wound tissue causes delays in wound healing in this population. We hypothesized that exercise in obese mice would speed wound healing and reduce tissue inflammation as measured by inflammatory gene expression. Methods: Mice were fed a 45% kcal from fat diet for 16 weeks, then treadmill exercised for 3 days prior and 5 days after application of full-thickness punch biopsy wounds. Wounds were assessed daily for wound area via photoplanimetry. In a separate study, wound were harvested from mice at 1, 3, or 5 days
Virginia Tech, 237 Wallace Hall (0426), Blacksburg, VA 24061, USA Caregiving-related stressors affect a variety of health indicators, including cardiovascular factors, insulin resistance and stress hormones, placing family caregivers at risk for poorer health and increased rates of morbidity and mortality. Researchers have speculated that the mechanism by which stressors lead to changes in health is through the collective upset of allostatic processes. The body’s ability to achieve stability in response to stressful events is vital. Day-to-day stressors of living with someone who has mild cognitive impairment (MCI) may allow little time for recovery, thus interfering with allostatic processes. Using 7 days of diary interviews from 30 spousal care partners and 4 days of saliva samples (5 occasions per day), we document accounts of the daily frequency and intensity of early memory loss symptoms and behaviors of their partner with MCI. Specifically, we assess the association of MCIrelated symptoms and care needs with care partners’ daily psychological well being and the diurnal cortisol rhythm and alpha-amylase (sAA) rhythm. Multilevel models revealed daily variability and change in psychological affect and diurnal rhythms of cortisol and sAA. Daily primary stressors, everyday secondary strains, and marital interactions predicted changes in psychological affect. Daily stressors predicted differences in cortisol but not sAA rhythms. Conversely, daily marital interactions predicted differences in the sAA but not cortisol rhythms. Findings provide new details on previously masked causes of psychological and biological distress.
doi:10.1016/j.bbi.2011.07.116
114. Neuropeptide Y Y1 receptor, IL-1 receptor type I, and badrenergic receptors modulate P. gingivalis-induced inflammation B.F. Reader a,b,c, C.O. Igboin c, E.J. Leys c, M.T. Bailey a,c, B. Leblebicioglu d, J.F. Sheridan a,b,c a Institute for Behavioral Medicine Research, College of Medicine, The Ohio State University, Columbus, OH 43210, USA b Integrated Biomedical Science Graduate Program, College of Medicine, USA c Section of Oral Biology, College of Dentistry, USA d Department of Periodontology, College of Dentistry, USA
PNIRS meeting abstracts / Brain, Behavior, and Immunity 25 (2011) S179–S242
107. Elevated salivary C-reactive protein in maltreated children A. Danese, I. Ouellet-Morin, L. Arseneault
gle dose of treatment in our model; we are currently investigating which mechanism is involved in such effect.
Institute of Psychiatry, King’s College London, 16 DeCrespigny Park, London, SE5 8AF, Great Britain and Northern Ireland, UK
doi:10.1016/j.bbi.2011.07.111
Background: Childhood maltreatment is linked to elevated inflammation levels in adult life. There is only initial evidence suggesting that these life-course effects emerge in childhood years. We aimed to expand previous evidence by measuring inflammation levels in maltreated children using a newly validated non-invasive assay for C-reactive protein (CRP) in saliva. Methods: Participants were recruited from the E-Risk Longitudinal Twin Study, which tracks the development of a nationally-representative birth cohort of 2232 British children. From the total E-Risk sample, we identified 190 12-year-old identical twins eligible to participate in a sub-study of stress biology. Maltreatment was prospectively assessed through validated interviews with mothers. Inflammation was measured through salivary CRP. Results: Analyses adjusted for sex, age, pubertal stage, and anti-inflammatory medication use showed that maltreated children exhibited elevated salivary CRP levels compared to non-maltreated children (p = .021). The elevated inflammation levels observed in maltreated children were not explained by BMI, socio-economic status, and depressive symptoms. Conclusion: Maltreated children show elevated inflammation levels already at age 12 years. Therefore, interventions to prevent the long-term effects of childhood maltreatment on adult mental and physical health should start in childhood. doi:10.1016/j.bbi.2011.07.110
108. Cannabidiol produces a long-term anti-inflammatory effect in a murine model of acute lung injury A. Ribeiro a, V. Ferraz-de-Paula a, M.L. Pinheiro a, W.M. Quinteiro-Filho a, A.T. Akamine a, V.I. Almeida a, A. Zager a, J.E. Hallak b, A.W. Zuardi b, J.A. Crippa b, J. Palermo-Neto a a School of Veterinary Medicine, University of Sao Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, Sao Paulo, Sao Paulo 05508-270, Brazil b Department of Neuroscience and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, Brazil
Endocannabinoid system has become a topic of great interest in pharmacology. Therefore, we analyzed long-term effects of cannabidiol in a murine model of acute lung injury. C57BL/6 male mice were divided randomly in three groups, vehicle + PBS (veh + PBS), vehicle + LPS (veh + LPS) and cannabidiol + LPS CBD + LPS (CBD 20 mg/ kg). Mice were treated (i.p.) with vehicle or CBD and 60 min later received intranasal (i.n.) instillation of LPS or sterile PBS. One, two, four, and seven days later mice were killed by exsanguination and bronchoalveolar lavage fluid (BAL) was collected to measure total cell count and cytokine/chemokine production and lung was harvested to analyze leukocyte infiltration (hematoxylin/eosin staining). We observed that on day 1, 2 and 4 total cell count in the BAL was increased (p < .05) in the veh + LPS group and CBD prevented such increase by 50% (p < .05). We also observed that CBD modulates cytokine/chemokine production quantified in the BAL: on day 1 and 2 we observed that CBD treatment prevented MIP-2, TNF, and IL-6 increasing (p < .05); additionally, a tendency towards decreasing MCP-1 on day 1 and 2 (p = .1) and increasing IL-10 on day 2 (p = .1) was verified. Finally, we observed that CBD treatment prevented mainly neutrophil migration into the lungs. Thus, we show that CBD has a long-term anti-inflammatory effect with a sin-
109. Individual variation in inflammatory physiology: Modulation by serotonin W. Amaral a, G. Lubach a, A. Bennett b, C. Coe a a
The University of Wisconsin-Madison, Harlow Center for Biological Psychology, 22 N. Charter Street, Madison, WI 53715, USA b Wake Forest University Health Sciences, USA Our study used a nonhuman primate model to investigate whether a functional length polymorphism in the promoter of the serotonin transporter gene, 5-HTTLPR, helps to explain individual variation in proinflammatory immune responses. In the nervous system, the serotonin transporter regulates uptake of 5HT from the synaptic cleft following release and therefore affects serotonergic efficiency. The short 5-HTTLPR variant that acts as a dominant allele, is characterized by lower transcription rates, reduced uptake and increased extracellular 5HT, and has been associated with emotional reactivity and depression. Serotonin is also present in the gut and blood compartments, where it influences vessel permeability, cell trafficking, and inflammatory responses of leukocytes. Twenty juvenile male rhesus monkeys were genotyped and cytokine release characterized after overnight stimulation of blood cultures with LPS. The amount of IL-6 in the supernatant was also compared when the cells were pretreated with 5HT before adding LPS to the wells. A secondary goal was also to determine if a monkey’s genotype and inflammatory bias was associated with either its dominance status in the social groups comprised of 4–6 animals or its temperament, Our findings extend the significance of 5HT from its role as a neurotransmitter to its function as modulator of inflammation in the periphery, where high rather than low levels would be associated with greater emotionality. doi:10.1016/j.bbi.2011.07.112
110. Age-related increase in microglia proliferation in the hippocampus R.A. Kohman, E.K. DeYoung, J.S. Rhodes Department of Psychology, University of Illinois, Beckman Institute, Urbana, IL 61801, USA Aging is associated with neuroinflammation that may contribute to cognitive deficits and reductions in neural plasticity. The enhanced neuroinflammation is attributed to increased expression of inflammatory mediators by microglia, but increased proliferation may also contribute. Prior in vitro work indicates that aging increases microglia proliferation (Rozovsky et al., 1998). The current study evaluated the effects of aging on microglia proliferation within the hippocampus and whether exercise modulates the proliferation and/or activation state of microglia, as microglia can acquire an inflammatory or neuroprotective phenotype. We also assessed hippocampal neurogenesis to determine whether changes in microglia were associated with neuron survival. Adult (3.5 months) and aged (18 months) male BALB/c mice were individually housed with or without running wheels for 8 weeks. During the initial ten days, mice received Bromodeoxyuridine injections to label dividing cells.
PNIRS meeting abstracts / Brain, Behavior, and Immunity 25 (2011) S179–S242
Immunofluorescence was conducted to measure microglia proliferation, insulin-like growth factor (IGF) expression, and neuron survival. Expression of the trophic factor IGF was assessed as an indication of alternative activation. Results show that microglia proliferation was increased in aged mice, which exercise tended to reduce. Exercise enhanced survival of new neurons in both age groups. Though still in progress, we hypothesize a reduction in IGF expressing microglia in aged mice. Ultimately, findings will further our understanding of how exercise modulates neuroimmune activity and the potential influence on neural plasticity. doi:10.1016/j.bbi.2011.07.113
S211
post-wounding and assessed for inflammation via RT-PCR analysis of inflammation-related gene expression. Results: Exercise sped wound healing rate in obese mice compared to sedentary controls over the first 5 days post-wounding (p = .05). Although wound inflammation was not statistically different (p > .05), exercise resulted in an approximately 1.5 to 2.5-fold induction in the gene expression of F4/80, IL-10, TNF-alpha, CD206, and MCP-1 in the wound tissue at day 1 post-wounding. Conclusion: Contrary to our hypothesis, inflammation in exercise mice tended to be higher at 1 day postwounding. Additionally, markers of alternative activation of macrophages were upregulated. These data suggest a role for exercise in speeding the inflammatory process and altering the phenotype of inflammatory cells to one which promotes healing.
111. Stress, autonomic nervous system imbalance and psychopathology A. Halaris, E. Meresh, J. Fareed, S. Kimmons, J. Sinacore, N. Ruys
doi:10.1016/j.bbi.2011.07.115
Loyola University Stritch School of Medicine, Psychiatry, 2160 South First Avenue, Maywood, IL 60153, USA
113. Daily stressors and marital interactions affect diurnal cortisol and alpha-amylase rhythm in spouses of persons with mild cognitive impairment J.S. Savla, K.A. Roberto, R. Blieszner
Cardiovascular disease (CVD) and major depression (MDD) are two of the world’s leading health problems and they are highly interrelated. Repeated episodes of stress, anxiety, and depression can lead to a chronic pro-inflammatory status culminating in atherosclerosis and ultimately cardiovascular and cerebrovascular disease. Patients with MDD have higher levels of perceived stress compared to healthy controls. The harmful effects of chronic stress and depression on cardiovascular health have been documented for many years. Mental stress can result in a prolonged increase in aortic stiffness and can induce vascular stiffening even in young apparently healthy subjects with no traditional CVD risk factors. Psychological stress has been correlated with structural changes in arteries eventually leading to endothelial injury with atherothrombotic sequealae. Anxiety is a major risk factor for myocardial infarction (MI) and anxiety among initially healthy persons often predicts future acute MI or death due to cardiovascular disease, independent of other major risk factors. We conducted an open-label study comparing patients with MDD and matched healthy controls and sought to determine the level of stress perception before and after treatment with escitalopram. Additionally we assessed the degree of inflammation and arterial stiffness present in our subjects at pretreatment and whether the depressed patients showed normalization of inflammation biomarkers and arterial stiffness following successful treatment with escitalopram. doi:10.1016/j.bbi.2011.07.114
112. Effects of exercise on wound healing and wound tissue inflammation in obese mice B.D. Pence, S.A. Martin, J.A. Woods University of Illinois at Urbana-Champaign, 906 S Goodwin Ave, Urbana, IL 61801, USA Introduction: Impaired wound healing remains a major health concern for obese individuals. Studies show that prolonged inflammation in the wound tissue causes delays in wound healing in this population. We hypothesized that exercise in obese mice would speed wound healing and reduce tissue inflammation as measured by inflammatory gene expression. Methods: Mice were fed a 45% kcal from fat diet for 16 weeks, then treadmill exercised for 3 days prior and 5 days after application of full-thickness punch biopsy wounds. Wounds were assessed daily for wound area via photoplanimetry. In a separate study, wound were harvested from mice at 1, 3, or 5 days
Virginia Tech, 237 Wallace Hall (0426), Blacksburg, VA 24061, USA Caregiving-related stressors affect a variety of health indicators, including cardiovascular factors, insulin resistance and stress hormones, placing family caregivers at risk for poorer health and increased rates of morbidity and mortality. Researchers have speculated that the mechanism by which stressors lead to changes in health is through the collective upset of allostatic processes. The body’s ability to achieve stability in response to stressful events is vital. Day-to-day stressors of living with someone who has mild cognitive impairment (MCI) may allow little time for recovery, thus interfering with allostatic processes. Using 7 days of diary interviews from 30 spousal care partners and 4 days of saliva samples (5 occasions per day), we document accounts of the daily frequency and intensity of early memory loss symptoms and behaviors of their partner with MCI. Specifically, we assess the association of MCIrelated symptoms and care needs with care partners’ daily psychological well being and the diurnal cortisol rhythm and alpha-amylase (sAA) rhythm. Multilevel models revealed daily variability and change in psychological affect and diurnal rhythms of cortisol and sAA. Daily primary stressors, everyday secondary strains, and marital interactions predicted changes in psychological affect. Daily stressors predicted differences in cortisol but not sAA rhythms. Conversely, daily marital interactions predicted differences in the sAA but not cortisol rhythms. Findings provide new details on previously masked causes of psychological and biological distress.
doi:10.1016/j.bbi.2011.07.116
114. Neuropeptide Y Y1 receptor, IL-1 receptor type I, and badrenergic receptors modulate P. gingivalis-induced inflammation B.F. Reader a,b,c, C.O. Igboin c, E.J. Leys c, M.T. Bailey a,c, B. Leblebicioglu d, J.F. Sheridan a,b,c a Institute for Behavioral Medicine Research, College of Medicine, The Ohio State University, Columbus, OH 43210, USA b Integrated Biomedical Science Graduate Program, College of Medicine, USA c Section of Oral Biology, College of Dentistry, USA d Department of Periodontology, College of Dentistry, USA