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Abstract # 1864 Modafinil prevents sickness behavior induced by LPS in mice: Role for dopaminergic D1 receptor
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Abstracts / Brain, Behavior, and Immunity 57 (2016) e1–e43
pro-inflammatory cytokines were assessed at baseline and 1.5 h post injection. Current SRH (‘‘How is your health right now”) and general SRH (‘‘How is your general health?”) was measured 1.5 h post injection. Using path analysis, we tested the hypothesis that LPSincreased inflammation provokes sickness behavior, which in turn results in worsened SRH. SRH deteriorated 1.5 h after LPS injection (general: b = .44, p < .001; current: b = .61, p < .001) and these effects were statistically mediated by sickness behavior (general SRH: b = .28, p = .02; current SRH: b = .39, p = .02). However, having a stronger inflammatory response was a significant mediator for worsened current health only (p < 0.01). Whereas the observed deterioration in current health would be expected during immune provocation, the present study implies that individuals also rate their general health condition as less favorable during an ongoing inflammation, and that they do this as a consequence of sickness behavior. http://dx.doi.org/10.1016/j.bbi.2016.07.137
Abstract # 1862 Indoleamine-2,3-dioxgenase 1 (Ido1) protects against viral encephalitis M. Juda, A.K. Brooks, A. Towers, G.G. Freund, R.H. McCusker, A.J. Steelman University of Illinois Urbana-Champaign, Champaign, United States Viral encephalitis (VE) is a life-threatening condition that can be triggered by infection with a multitude of different viruses including members of Picornaviridae. There are few treatment options for VE and the mechanisms that influence prognosis are poorly defined. Inhibition of Ido1 aids in viral clearance during experimental West Nile Virus encephalitis. To determine the role of Ido1 during picornavirus-induced encephalitis we inoculated wild-type (WT) and Ido1-/- mice with either vehicle or Theiler’s murine encephalomyelitis virus. Anxiety-like behavior was measured using an elevated zero maze at day 6 post-infection (p.i.). Burrowing activity was measured at days 4 and 6 p.i. Hippocampal gene expression was determined by RT-qPCR. Infected Ido1-/- mice showed a tendency toward a higher incidence of seizures (50% vs. 69.6%; p = 0.06). The occurrence of seizures was associated with greater time spent in the open areas of the maze, suggesting reduced anxiety. Infected Ido1-/- mice entered the light zone more often than WT mice. However, infection reduced burrowing activity and infected Ido1-/- mice burrowed less than WT mice. Infection increased Ido1, Ifng and viral RNA expression. The elevation in Ifng and viral RNA expression was greater in Ido1-/- compared to WT mice at day 8 p.i. These data indicate that Ido1 impedes viral replication, decreases neuroinflammation, and modulates encephalitisinduced behavioral alterations. Thus, the absence of Ido1 during picornavirus-induced encephalitis may be detrimental. http://dx.doi.org/10.1016/j.bbi.2016.07.138
Abstract # 1863 What your monocytes’ inflammatory responses to adrenergic stimulation can tell you about your risk for cardiovascular disease beyond blood pressure S.I. Dimitrov a, F. Sheikh a, J. Green a, T. Cheng a, N. Beg a, S. Hong a,b
a University of California San Diego, Department of Psychiatry, 9500 Gilman Dr., La Jolla, CA 92093, United States b Department of Family Medicine & Public Health, United States
Pathophysiology of hypertension includes hyperactive sympathoadrenal system and elevated inflammation, but the link between the two and its clinical risk remain unclear. Subclinically elevated blood pressure (BP), pre-hypertension (PHT), is related to future cardiovascular disease (CVD) and greater mortality. In 177 adults with PHT (125 < SBP < 140 mmHg, n = 66) versus normal BP (NBP, n = 105), we investigated the association between monocytes’ sensitivity to isoproterenol control of LPS-induced TNF production using flow cytometry and CV risk calculated using Framingham risk score (FRS) for CVD. FRSs, either factoring in BMI or lipid levels, were greater in PHT than NBP group (p0 s < .001). Beta-adrenergic-recep tor-mediated inflammation control (‘‘BARIC”) by monocytes was lower in PHT than NBP group (p<.01). Curiously, BARIC was correlated with the FRS (r = .22 to .25, p0 s < .05) in NBP, but not in PHT group (r = .10 to .20). Our results indicate that even mildly elevated BP is related to impaired inflammation regulation mediated by sympathoadrenal over-activation. Meanwhile, the characteristics of the associations of BP vs. inflammation regulation to CVD risk appear different. http://dx.doi.org/10.1016/j.bbi.2016.07.139
Abstract # 1864 Modafinil prevents sickness behavior induced by LPS in mice: Role for dopaminergic D1 receptor A. Zager a, R.O. Margatho a, W.N. Brandão a, J. Peron a, M.L. Andersen b, J. Palermo-Neto a a
Orlando Marques Paiva, 87, School of Veterinary Medicine, University of Sao Paulo, Sao Paulo, SP 05508-270, Brazil b Federal University of Sao Paulo, Brazil Modafinil is a psychostimulant drug that is used to treat Narcolepsy and Excessive Daytime Sleepiness, due to a dopaminerelated action. Recent studies indicated that Modafinil prevents inflammation in animal models of neurodegeneration. However, the effect of Modafinil on the behavioral changes induced by systemic inflammation is still unknown. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced sickness behavior, and determine the role of dopaminergic D1 receptor in this phenomenon. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil and, 30 min later, received a single saline or LPS administration, followed by open field and elevated plus maze test 2 h later. Modafinil treatment prevented the LPS-induced increases in immobility and anxiety-like behavior. The pharmacological blockage of the dopaminergic D1R by the drug SCH-23390 counteracted the preventive effect of Modafinil on locomotion and anxiety-like behavior. Our results indicate that Modafinil pretreatment prevented the behavioral inhibition of an acute LPS challenge. The dopaminergic D1 receptor signaling is essential to the Modafinil effects on locomotion and anxiety. This evidence suggests that Modafinil treatment may be useful to prevent inflammation-related behavioral inhibition, possibly due to a neuroimmune mechanism. http://dx.doi.org/10.1016/j.bbi.2016.07.140
Abstracts / Brain, Behavior, and Immunity 57 (2016) e1–e43
pro-inflammatory cytokines were assessed at baseline and 1.5 h post injection. Current SRH (‘‘How is your health right now”) and general SRH (‘‘How is your general health?”) was measured 1.5 h post injection. Using path analysis, we tested the hypothesis that LPSincreased inflammation provokes sickness behavior, which in turn results in worsened SRH. SRH deteriorated 1.5 h after LPS injection (general: b = .44, p < .001; current: b = .61, p < .001) and these effects were statistically mediated by sickness behavior (general SRH: b = .28, p = .02; current SRH: b = .39, p = .02). However, having a stronger inflammatory response was a significant mediator for worsened current health only (p < 0.01). Whereas the observed deterioration in current health would be expected during immune provocation, the present study implies that individuals also rate their general health condition as less favorable during an ongoing inflammation, and that they do this as a consequence of sickness behavior. http://dx.doi.org/10.1016/j.bbi.2016.07.137
Abstract # 1862 Indoleamine-2,3-dioxgenase 1 (Ido1) protects against viral encephalitis M. Juda, A.K. Brooks, A. Towers, G.G. Freund, R.H. McCusker, A.J. Steelman University of Illinois Urbana-Champaign, Champaign, United States Viral encephalitis (VE) is a life-threatening condition that can be triggered by infection with a multitude of different viruses including members of Picornaviridae. There are few treatment options for VE and the mechanisms that influence prognosis are poorly defined. Inhibition of Ido1 aids in viral clearance during experimental West Nile Virus encephalitis. To determine the role of Ido1 during picornavirus-induced encephalitis we inoculated wild-type (WT) and Ido1-/- mice with either vehicle or Theiler’s murine encephalomyelitis virus. Anxiety-like behavior was measured using an elevated zero maze at day 6 post-infection (p.i.). Burrowing activity was measured at days 4 and 6 p.i. Hippocampal gene expression was determined by RT-qPCR. Infected Ido1-/- mice showed a tendency toward a higher incidence of seizures (50% vs. 69.6%; p = 0.06). The occurrence of seizures was associated with greater time spent in the open areas of the maze, suggesting reduced anxiety. Infected Ido1-/- mice entered the light zone more often than WT mice. However, infection reduced burrowing activity and infected Ido1-/- mice burrowed less than WT mice. Infection increased Ido1, Ifng and viral RNA expression. The elevation in Ifng and viral RNA expression was greater in Ido1-/- compared to WT mice at day 8 p.i. These data indicate that Ido1 impedes viral replication, decreases neuroinflammation, and modulates encephalitisinduced behavioral alterations. Thus, the absence of Ido1 during picornavirus-induced encephalitis may be detrimental. http://dx.doi.org/10.1016/j.bbi.2016.07.138
Abstract # 1863 What your monocytes’ inflammatory responses to adrenergic stimulation can tell you about your risk for cardiovascular disease beyond blood pressure S.I. Dimitrov a, F. Sheikh a, J. Green a, T. Cheng a, N. Beg a, S. Hong a,b
a University of California San Diego, Department of Psychiatry, 9500 Gilman Dr., La Jolla, CA 92093, United States b Department of Family Medicine & Public Health, United States
Pathophysiology of hypertension includes hyperactive sympathoadrenal system and elevated inflammation, but the link between the two and its clinical risk remain unclear. Subclinically elevated blood pressure (BP), pre-hypertension (PHT), is related to future cardiovascular disease (CVD) and greater mortality. In 177 adults with PHT (125 < SBP < 140 mmHg, n = 66) versus normal BP (NBP, n = 105), we investigated the association between monocytes’ sensitivity to isoproterenol control of LPS-induced TNF production using flow cytometry and CV risk calculated using Framingham risk score (FRS) for CVD. FRSs, either factoring in BMI or lipid levels, were greater in PHT than NBP group (p0 s < .001). Beta-adrenergic-recep tor-mediated inflammation control (‘‘BARIC”) by monocytes was lower in PHT than NBP group (p<.01). Curiously, BARIC was correlated with the FRS (r = .22 to .25, p0 s < .05) in NBP, but not in PHT group (r = .10 to .20). Our results indicate that even mildly elevated BP is related to impaired inflammation regulation mediated by sympathoadrenal over-activation. Meanwhile, the characteristics of the associations of BP vs. inflammation regulation to CVD risk appear different. http://dx.doi.org/10.1016/j.bbi.2016.07.139
Abstract # 1864 Modafinil prevents sickness behavior induced by LPS in mice: Role for dopaminergic D1 receptor A. Zager a, R.O. Margatho a, W.N. Brandão a, J. Peron a, M.L. Andersen b, J. Palermo-Neto a a
Orlando Marques Paiva, 87, School of Veterinary Medicine, University of Sao Paulo, Sao Paulo, SP 05508-270, Brazil b Federal University of Sao Paulo, Brazil Modafinil is a psychostimulant drug that is used to treat Narcolepsy and Excessive Daytime Sleepiness, due to a dopaminerelated action. Recent studies indicated that Modafinil prevents inflammation in animal models of neurodegeneration. However, the effect of Modafinil on the behavioral changes induced by systemic inflammation is still unknown. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced sickness behavior, and determine the role of dopaminergic D1 receptor in this phenomenon. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil and, 30 min later, received a single saline or LPS administration, followed by open field and elevated plus maze test 2 h later. Modafinil treatment prevented the LPS-induced increases in immobility and anxiety-like behavior. The pharmacological blockage of the dopaminergic D1R by the drug SCH-23390 counteracted the preventive effect of Modafinil on locomotion and anxiety-like behavior. Our results indicate that Modafinil pretreatment prevented the behavioral inhibition of an acute LPS challenge. The dopaminergic D1 receptor signaling is essential to the Modafinil effects on locomotion and anxiety. This evidence suggests that Modafinil treatment may be useful to prevent inflammation-related behavioral inhibition, possibly due to a neuroimmune mechanism. http://dx.doi.org/10.1016/j.bbi.2016.07.140