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Characterization of in vitro leukocyte maximal telomerase activity capacity (mTAC) in humans: Association with chronic stress exposure and stress-reactivity
Abstracts / Brain, Behavior, and Immunity 66 (2017) e1–e42
exposure led to aberrant CEC signaling. Mice were exposed to social disruption (SDR), involving repeated social defeat for 2 h a night on 6 consecutive nights. The morning following the last night of SDR, the colonic microbiome was assessed using 16s rRNA gene sequencing. Colons were also excised for CEC isolation, purification, and RNA extraction for next generation RNA sequencing (RNAseq) to characterize the CEC transcriptome profile. Results demonstrated that CECs are highly active during SDR-exposure as evidenced by significant changes in over 500 genes, including increases in antimicrobial peptides, e.g., RegIIIgamma, inflammatory mediators, e.g., iNOS, TNF signaling, and serum amyloid A, and chemokines, e.g., CXCL2. Significant increases in genes such as Duox, known to be induced by microbial dysbiosis, support the hypothesis that stressorinduced microbial changes contribute to dysregulation of CEC activity. Increased transcription of inflammation-related genes indicates that CEC play a role in stressor-induced exacerbation of colonic inflammation. http://dx.doi.org/10.1016/j.bbi.2017.07.069
Abstract # 1933 Characterization of in vitro leukocyte maximal telomerase activity capacity (mTAC) in humans: Association with chronic stress exposure and stress-reactivity K. de Punder a, C. Heim a,b, I. Przesdzing c, P.D. Wadhwa d, S. Entringer a,d a Charité – Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany b Department of Biobehavioral Health, College of Health and Human Development, Pennsylvania State University, Pennsylvania, USA c Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Experimental Neurology and Center for Stroke Research Berlin (CSB), Berlin, Germany d Development, Health and Disease Research Program, University of California, Irvine, School of Medicine, Irvine, CA, USA
Shorter leukocyte telomere length is associated with the occurrence and progression of several stress-related disorders. The cellular reverse transcriptase enzyme telomerase can counteract telomere shortening and preserve healthy cell function. Studies on stress exposure and leukocyte telomerase activity (TA) have yielded inconclusive results, perhaps, in part, because TA is dynamic in nature and expressed in low amounts in resting immune cells. In contrast, leukocyte maximal TA capacity (mTAC) can be measured in vitro using a mitogen-stimulation protocol. The aim of this study was to establish within- subject stability and between-subject variability of mTAC across different conditions. mTAC was measured in leukocytes obtained from 28 healthy participants at different times of the day and before and after a standardized laboratory stress test. Overall, mTAC did not significantly change over the course of the day or in response to acute psychosocial stress. However, mTAC levels were negatively associated with chronic stress exposure (r = 0.43, p < 0.05) and the cortisol responses to the stress test (r = 0.46, p < 0.05). In conclusion, because mTAC is not influenced by acute circumstances, and shows substantial between- subject variability in relation to stress-related states and traits, this in vitro measure of TA may represent a potentially useful individual difference measure in stress-related studies of the human telomere biology system. http://dx.doi.org/10.1016/j.bbi.2017.07.070
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Abstract # 1934 Is inflammatory markers related with cognitive impairment in bipolar disorder? I.G. Barbosa a,b, R.A. Ferreira c, F.M. Leite c, G.C. Mol a,b,c, N.P. Rocha a,b,d, J. Salgado e,f, A.L. Teixeira a,b,d a
Laboratório Interdisciplinar de Investigação Médica (LIIM), Faculdade de Medicina Universidade Federal de Minas Gerais, Belo Horizonte, Brazil b Mental Health Departament, 190 Alfredo Balena Avenue, 218 Room, Belo Horizonte, Minas Gerais 30130-100, USA c Instituto de Previdência dos Servidores do Estado de Minas Gerais, Belo Horizonte, Brazil d Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston USA e Instituto Raul Soares, Belo Horizonte, Brazil f Universidade Federal de Minas Gerais, Brazil Background: Bipolar disorder (BD) diagnosis is based on specific set of mood and behavioural symptoms although they also exhibit cognitive dysfunction. Immune/inflammatory mechanisms have been implicated in the pathophysiology of BD. Objective: To investigate whether cognitive functioning is associated with clinical parameters and immune profile in patients with BD in remission. Methods: Twenty patients with BD type I in remission (15/20 female; age [mean SD] 43.80 11.72 years; years of education [mean SD] 12.40 3.39) and 25 healthy controls (16/25 female; age [mean SD] 43.52 11.72 years; years of education [mean SD] 11.16 2.66) matched for age, gender, and years of education were enrolled in this study. Subjects were evaluated with the Mini-Plus; Young Mania Rating Scale; Hamilton Depression Rating Scale; and with Brief Assessment of Cognition in Affective Disorders a comprehensive test battery to evaluate visuomotor, immediate affective and non-affective memory, verbal fluency, delayed affective and non-affective memory, inhibition, and problem solving domains. We assessed IL2, IL4, IL6, IL10, IL17, INF, TNF and its soluble receptors in plasma by flow cytometry. Results: Patients with BD exhibited poorer performance on all cognitive domains in comparison with controls. Patients with BD also had high levels of soluble TNF receptors, and Th1/Th2/Th17 cytokines (p < 0.005). Poorer performance in executive function summary scores correlated positively with IL10 plasma levels. Conclusion: Our data suggest that inflammatory dysfunction might contribute to the cognitive impairment in BD. http://dx.doi.org/10.1016/j.bbi.2017.07.071
Abstract # 1935 Maltreatment is associated with elevated C-reactive protein levels in 3 to 5 year-old children K. de Punder a, J. Overfeld a,b, P. Dörr c, K. Dittrich c, S.M. Winter c, N. Kubiak a, G. Karaboycheva a, C. Heim a,d a Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany b Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin Center for Advanced Neuroimaging, Bernstein Center for Computational Neuroscience, Berlin, Germany
exposure led to aberrant CEC signaling. Mice were exposed to social disruption (SDR), involving repeated social defeat for 2 h a night on 6 consecutive nights. The morning following the last night of SDR, the colonic microbiome was assessed using 16s rRNA gene sequencing. Colons were also excised for CEC isolation, purification, and RNA extraction for next generation RNA sequencing (RNAseq) to characterize the CEC transcriptome profile. Results demonstrated that CECs are highly active during SDR-exposure as evidenced by significant changes in over 500 genes, including increases in antimicrobial peptides, e.g., RegIIIgamma, inflammatory mediators, e.g., iNOS, TNF signaling, and serum amyloid A, and chemokines, e.g., CXCL2. Significant increases in genes such as Duox, known to be induced by microbial dysbiosis, support the hypothesis that stressorinduced microbial changes contribute to dysregulation of CEC activity. Increased transcription of inflammation-related genes indicates that CEC play a role in stressor-induced exacerbation of colonic inflammation. http://dx.doi.org/10.1016/j.bbi.2017.07.069
Abstract # 1933 Characterization of in vitro leukocyte maximal telomerase activity capacity (mTAC) in humans: Association with chronic stress exposure and stress-reactivity K. de Punder a, C. Heim a,b, I. Przesdzing c, P.D. Wadhwa d, S. Entringer a,d a Charité – Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany b Department of Biobehavioral Health, College of Health and Human Development, Pennsylvania State University, Pennsylvania, USA c Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Department of Experimental Neurology and Center for Stroke Research Berlin (CSB), Berlin, Germany d Development, Health and Disease Research Program, University of California, Irvine, School of Medicine, Irvine, CA, USA
Shorter leukocyte telomere length is associated with the occurrence and progression of several stress-related disorders. The cellular reverse transcriptase enzyme telomerase can counteract telomere shortening and preserve healthy cell function. Studies on stress exposure and leukocyte telomerase activity (TA) have yielded inconclusive results, perhaps, in part, because TA is dynamic in nature and expressed in low amounts in resting immune cells. In contrast, leukocyte maximal TA capacity (mTAC) can be measured in vitro using a mitogen-stimulation protocol. The aim of this study was to establish within- subject stability and between-subject variability of mTAC across different conditions. mTAC was measured in leukocytes obtained from 28 healthy participants at different times of the day and before and after a standardized laboratory stress test. Overall, mTAC did not significantly change over the course of the day or in response to acute psychosocial stress. However, mTAC levels were negatively associated with chronic stress exposure (r = 0.43, p < 0.05) and the cortisol responses to the stress test (r = 0.46, p < 0.05). In conclusion, because mTAC is not influenced by acute circumstances, and shows substantial between- subject variability in relation to stress-related states and traits, this in vitro measure of TA may represent a potentially useful individual difference measure in stress-related studies of the human telomere biology system. http://dx.doi.org/10.1016/j.bbi.2017.07.070
e17
Abstract # 1934 Is inflammatory markers related with cognitive impairment in bipolar disorder? I.G. Barbosa a,b, R.A. Ferreira c, F.M. Leite c, G.C. Mol a,b,c, N.P. Rocha a,b,d, J. Salgado e,f, A.L. Teixeira a,b,d a
Laboratório Interdisciplinar de Investigação Médica (LIIM), Faculdade de Medicina Universidade Federal de Minas Gerais, Belo Horizonte, Brazil b Mental Health Departament, 190 Alfredo Balena Avenue, 218 Room, Belo Horizonte, Minas Gerais 30130-100, USA c Instituto de Previdência dos Servidores do Estado de Minas Gerais, Belo Horizonte, Brazil d Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston USA e Instituto Raul Soares, Belo Horizonte, Brazil f Universidade Federal de Minas Gerais, Brazil Background: Bipolar disorder (BD) diagnosis is based on specific set of mood and behavioural symptoms although they also exhibit cognitive dysfunction. Immune/inflammatory mechanisms have been implicated in the pathophysiology of BD. Objective: To investigate whether cognitive functioning is associated with clinical parameters and immune profile in patients with BD in remission. Methods: Twenty patients with BD type I in remission (15/20 female; age [mean SD] 43.80 11.72 years; years of education [mean SD] 12.40 3.39) and 25 healthy controls (16/25 female; age [mean SD] 43.52 11.72 years; years of education [mean SD] 11.16 2.66) matched for age, gender, and years of education were enrolled in this study. Subjects were evaluated with the Mini-Plus; Young Mania Rating Scale; Hamilton Depression Rating Scale; and with Brief Assessment of Cognition in Affective Disorders a comprehensive test battery to evaluate visuomotor, immediate affective and non-affective memory, verbal fluency, delayed affective and non-affective memory, inhibition, and problem solving domains. We assessed IL2, IL4, IL6, IL10, IL17, INF, TNF and its soluble receptors in plasma by flow cytometry. Results: Patients with BD exhibited poorer performance on all cognitive domains in comparison with controls. Patients with BD also had high levels of soluble TNF receptors, and Th1/Th2/Th17 cytokines (p < 0.005). Poorer performance in executive function summary scores correlated positively with IL10 plasma levels. Conclusion: Our data suggest that inflammatory dysfunction might contribute to the cognitive impairment in BD. http://dx.doi.org/10.1016/j.bbi.2017.07.071
Abstract # 1935 Maltreatment is associated with elevated C-reactive protein levels in 3 to 5 year-old children K. de Punder a, J. Overfeld a,b, P. Dörr c, K. Dittrich c, S.M. Winter c, N. Kubiak a, G. Karaboycheva a, C. Heim a,d a Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin, Germany b Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin Center for Advanced Neuroimaging, Bernstein Center for Computational Neuroscience, Berlin, Germany