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Cannabidiol produces a long-term anti-inflammatory effect in a murine model of acute lung injury
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
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.