- Email: [email protected]
Depressive mood is correlated with increased IL-6 and IL-1RA before but not after an acute exercise stressor
Abstracts / Brain, Behavior, and Immunity 24 (2010) S1–S71
social stress induced two behavioural profiles in BALB/c mice; stresssusceptible and stress-resistant, correlating with an increase in corticosterone (stress hormone) and pro-inflammatory cytokines in susceptible mice. Both mouse strains responded to chronic social defeat stress, displaying social avoidance and decreased corticosterone compared to unstressed control mice. However, both strains were resistant to early-life stress. Therefore, both social stresses could induce different IBS-like symptoms, representing new promising tools to investigate IBS using mice. This strengthens the multifactorial, i.e. stress and genetic contribution to IBS, and may better represent the differing aetiologies underlying IBS symptoms observed in patients. doi:10.1016/j.bbi.2010.07.187
Abstract # 453 A comparative study of CNS effects of LPS and pro-inflammatory cytokines D. Skelly, E. Hennessy, C. Cunningham Trinity College Institute of Neuroscience, Dublin, Ireland The sickness behaviour and CNS inflammation induced by systemic lipopolysaccharide (LPS) and IL-1Beta are well characterised. However, the CNS effects of systemic TNF-Alpha and IL-6 have been less studied and comparisons of LPS, IL-1Beta, TNF-Alpha and IL-6 are lacking. Here, we challenged female C57BL/6 mice intraperitoneally with LPS (100 lg/kg), IL-1Beta (15 or 50 lg/kg), TNF-Alpha (50 or 250 lg/kg) or IL-6 (50 or 125 lg/kg). We investigated effects on open field activity, core body temperature, plasma levels of pro-inflammatory cytokines (IL-1Beta, TNF-Alpha, and IL-6), and corticosterone and prostaglandin E2 at 2 h post injection. We also examined levels of hippocampal and hypothalamic inflammatory cytokine transcripts (IL-1Beta, TNF-Alpha, activation (IL-6 and IFN-Beta) and markers of endothelial and microglial VCAM, COX-2 and uPAR). There were differential effects of inflammatory stimuli on open field activity and core body temperature (LPS, IL-1Beta > TNF-Alpha > IL-6). Levels of inflammatory markers in plasma and the CNS show a broadly similar response to LPS, IL-1Beta and TNF-Alpha. Injection of IL-1Beta i.p. induced plasma IL-6 but IL-6 i.p. did not induce plasma IL-1Beta. Furthermore, IL-6 failed to induce TNF-Alpha or corticosterone and was limited in its ability to induce CNS transcripts, with the exception of minor IL-1Beta increases. These data have implications for the frequent correlation of plasma IL-6 with deleterious CNS effects and for studies of the impact of systemic TNF-Alpha on neurodegeneration. doi:10.1016/j.bbi.2010.07.188
Abstract # 454 The role of herpes simplex virus type 1 in Alzheimer’s disease: Potential for treatment with antivirals R.F. Itzhaki, A.L. Frost, M.A. Wozniak Stopford Building Room 3.545, Faculty of Life Sciences, University of Manchester, Manchester, Lancs M13 9PT, Great Britain and Northern Ireland, UK
S57
The causes of Alzheimer’s disease (AD) are unknown. We have implicated herpes simplex virus type 1 (HSV1) as a major factor, on discovering that it resides latently in many elderly brains (J. Med. Virol., 1991, et seq.), that in carriers of the type 4 allele of the apolipoprotein E gene (APOE-e4) it confers a strong risk of AD (Lancet, 1997), and that it reactivates in brain, possibly recurrently (J. Med. Virol., 2005). Recently, we linked HSV1 directly to the abnormal features of AD brain, infection causing intracellular deposition of beta amyloid (Abeta), in cultured cells and in mouse brain (Neurosci. Lett., 2007); formation of AD-like tau in cultured cells (J Alz. Dis., 2009). Further, in AD brains, 90% of plaques contain HSV1 DNA and 72% of the viral DNA is located within plaques (in aged normal subjects, only 24%, possibly reflecting lesser Abeta production or better clearance) (J. Pathol., 2009). This specific co-localization, and the HSV1-induced Abeta deposition, strongly implicates HSV1 in the formation of toxic Abeta products and plaques. Our data point to the usage of antiviral agents to treat AD. These would inhibit all viral damage, not merely the formation of AD biomarkers. We have found that in HSV1-infected cell cultures the antiviral agent acyclovir greatly reduces Abeta deposition and AD-like tau, substantiating its proposed use for AD patients.
doi:10.1016/j.bbi.2010.07.189
Abstract # 455 Depressive mood is correlated with increased IL-6 and IL-1RA before but not after an acute exercise stressor J. Hallam, Y. Sim, J. Darling, N. Thompson, K. Warren, M. Kohut Iowa State University, 283 Forker, Ames, IA 50011, USA In an effort to determine the associations between inflammation, neuroendocrine factors and mood state, an inflammatory response was induced in 12 young male subjects by participating in a 2 week intense exercise program. Subjects completed the POMS questionnaire and a muscle soreness scale (as subjective measure of inflammation). Blood was collected prior to, during and 24 and 48 h after the 2 week intervention. Epinephrine, norepinephrine, cortisol, IL1Ra, IL-6, IL-10 and white blood cell populations were measured. The results showed that muscle soreness was correlated with increased IL-1Ra and decreased IL-10 in the post-exercise phase. Prior to the intervention, greater levels of IL-1Ra, IL-6, and absolute neutrophil counts were significantly correlated with higher depressive mood scores throughout all subsequent time points. Immediately following exercise stress, IL-6, IL-1Ra, and IL-10 increased significantly, but post-stress there was no association with depressive mood. In the recovery/repair phase (24 and 48 h post-intervention), an inverse correlation between depressive mood and IL-10 was found. No associations between norepinephrine, epinephrine, cortisol, and IL-6 or IL-1Ra were found, however, higher epinephrine levels at baseline were associated with greater IL-10 at all time points. Taken together, these findings suggest that depressive mood is correlated with increased IL-6 and IL-1Ra, but immediately following an acute stressor, this relationship is not observed. In the inflammatory repair phase, greater IL-10 is found in association with reduced depressive mood. doi:10.1016/j.bbi.2010.07.190
social stress induced two behavioural profiles in BALB/c mice; stresssusceptible and stress-resistant, correlating with an increase in corticosterone (stress hormone) and pro-inflammatory cytokines in susceptible mice. Both mouse strains responded to chronic social defeat stress, displaying social avoidance and decreased corticosterone compared to unstressed control mice. However, both strains were resistant to early-life stress. Therefore, both social stresses could induce different IBS-like symptoms, representing new promising tools to investigate IBS using mice. This strengthens the multifactorial, i.e. stress and genetic contribution to IBS, and may better represent the differing aetiologies underlying IBS symptoms observed in patients. doi:10.1016/j.bbi.2010.07.187
Abstract # 453 A comparative study of CNS effects of LPS and pro-inflammatory cytokines D. Skelly, E. Hennessy, C. Cunningham Trinity College Institute of Neuroscience, Dublin, Ireland The sickness behaviour and CNS inflammation induced by systemic lipopolysaccharide (LPS) and IL-1Beta are well characterised. However, the CNS effects of systemic TNF-Alpha and IL-6 have been less studied and comparisons of LPS, IL-1Beta, TNF-Alpha and IL-6 are lacking. Here, we challenged female C57BL/6 mice intraperitoneally with LPS (100 lg/kg), IL-1Beta (15 or 50 lg/kg), TNF-Alpha (50 or 250 lg/kg) or IL-6 (50 or 125 lg/kg). We investigated effects on open field activity, core body temperature, plasma levels of pro-inflammatory cytokines (IL-1Beta, TNF-Alpha, and IL-6), and corticosterone and prostaglandin E2 at 2 h post injection. We also examined levels of hippocampal and hypothalamic inflammatory cytokine transcripts (IL-1Beta, TNF-Alpha, activation (IL-6 and IFN-Beta) and markers of endothelial and microglial VCAM, COX-2 and uPAR). There were differential effects of inflammatory stimuli on open field activity and core body temperature (LPS, IL-1Beta > TNF-Alpha > IL-6). Levels of inflammatory markers in plasma and the CNS show a broadly similar response to LPS, IL-1Beta and TNF-Alpha. Injection of IL-1Beta i.p. induced plasma IL-6 but IL-6 i.p. did not induce plasma IL-1Beta. Furthermore, IL-6 failed to induce TNF-Alpha or corticosterone and was limited in its ability to induce CNS transcripts, with the exception of minor IL-1Beta increases. These data have implications for the frequent correlation of plasma IL-6 with deleterious CNS effects and for studies of the impact of systemic TNF-Alpha on neurodegeneration. doi:10.1016/j.bbi.2010.07.188
Abstract # 454 The role of herpes simplex virus type 1 in Alzheimer’s disease: Potential for treatment with antivirals R.F. Itzhaki, A.L. Frost, M.A. Wozniak Stopford Building Room 3.545, Faculty of Life Sciences, University of Manchester, Manchester, Lancs M13 9PT, Great Britain and Northern Ireland, UK
S57
The causes of Alzheimer’s disease (AD) are unknown. We have implicated herpes simplex virus type 1 (HSV1) as a major factor, on discovering that it resides latently in many elderly brains (J. Med. Virol., 1991, et seq.), that in carriers of the type 4 allele of the apolipoprotein E gene (APOE-e4) it confers a strong risk of AD (Lancet, 1997), and that it reactivates in brain, possibly recurrently (J. Med. Virol., 2005). Recently, we linked HSV1 directly to the abnormal features of AD brain, infection causing intracellular deposition of beta amyloid (Abeta), in cultured cells and in mouse brain (Neurosci. Lett., 2007); formation of AD-like tau in cultured cells (J Alz. Dis., 2009). Further, in AD brains, 90% of plaques contain HSV1 DNA and 72% of the viral DNA is located within plaques (in aged normal subjects, only 24%, possibly reflecting lesser Abeta production or better clearance) (J. Pathol., 2009). This specific co-localization, and the HSV1-induced Abeta deposition, strongly implicates HSV1 in the formation of toxic Abeta products and plaques. Our data point to the usage of antiviral agents to treat AD. These would inhibit all viral damage, not merely the formation of AD biomarkers. We have found that in HSV1-infected cell cultures the antiviral agent acyclovir greatly reduces Abeta deposition and AD-like tau, substantiating its proposed use for AD patients.
doi:10.1016/j.bbi.2010.07.189
Abstract # 455 Depressive mood is correlated with increased IL-6 and IL-1RA before but not after an acute exercise stressor J. Hallam, Y. Sim, J. Darling, N. Thompson, K. Warren, M. Kohut Iowa State University, 283 Forker, Ames, IA 50011, USA In an effort to determine the associations between inflammation, neuroendocrine factors and mood state, an inflammatory response was induced in 12 young male subjects by participating in a 2 week intense exercise program. Subjects completed the POMS questionnaire and a muscle soreness scale (as subjective measure of inflammation). Blood was collected prior to, during and 24 and 48 h after the 2 week intervention. Epinephrine, norepinephrine, cortisol, IL1Ra, IL-6, IL-10 and white blood cell populations were measured. The results showed that muscle soreness was correlated with increased IL-1Ra and decreased IL-10 in the post-exercise phase. Prior to the intervention, greater levels of IL-1Ra, IL-6, and absolute neutrophil counts were significantly correlated with higher depressive mood scores throughout all subsequent time points. Immediately following exercise stress, IL-6, IL-1Ra, and IL-10 increased significantly, but post-stress there was no association with depressive mood. In the recovery/repair phase (24 and 48 h post-intervention), an inverse correlation between depressive mood and IL-10 was found. No associations between norepinephrine, epinephrine, cortisol, and IL-6 or IL-1Ra were found, however, higher epinephrine levels at baseline were associated with greater IL-10 at all time points. Taken together, these findings suggest that depressive mood is correlated with increased IL-6 and IL-1Ra, but immediately following an acute stressor, this relationship is not observed. In the inflammatory repair phase, greater IL-10 is found in association with reduced depressive mood. doi:10.1016/j.bbi.2010.07.190