- Email: [email protected]
33. Programming of reproductive development by neonatal immunological challenge: Evidence for transgenerational inheritance
L. Sominsky et al. / Brain, Behavior, and Immunity 26 (2012) S1–S50
S9
uptake inhibitor, 2 mg/kg-daily injections during 5 days post-lesion), on the expression of tyrosine hydroxylase (TH), GFAP (astrocyte marker), and OX-42 (microglia marker), evaluated by immunohistochemistry and/or immunoblotting in the substancia nigra (SN) of rat brains unilaterally injected with 6-hydroxy-dopamine. The ACEA group exhibited a decrease about 30% in the TH levels and an increase about 24% in the OX-42 expression in relation to the control group (treated with vehicle DMSO). The AM404 group presented a decrease about 10% in the expression of TH and an increase about 20% and 26% in the expression of GFAP and OX-42, respectively, compared with the DMSO group. Our results show, therefore, that the treatment with both cannabinoid compounds seems to promote an increase in the microglial activation in the SN and an increment of TH-neurons lost induced by the 6-hydroxy-dopamine. This study adds information about the role of cannabinoid system and cannabinoid compounds as possible therapeutic tools in PD. FAPESP and CNPq.
ison group of TPO negative women (N = 72) was randomly selected. All women were visited monthly for 6 months by a research nurse blinded to TPO status. A blood sample was obtained and a targeted physical exam was done. Women completed a thyroid symptom checklist, the Perceived Stress Scale and the Profile of Mood States. The blood was tested at each visit for thyroid stimulating hormone (TSH) levels for all TPO positive women and any TPO negative women with enlarged thyroid glands or positive symptoms. Pregnant TPO positive women had statistically significant higher depressive symptoms and more clinical depression than TPO negative women. There was significantly higher depression, anger, and total mood disturbance scores throughout the postpartum for TPO positive women compared to TPO negative women. This occurred regardless of development of PPT. The study suggests that TPO autoantibodies alone, in pregnant and postpartum women increases the possibility of negative dysphoric mood states, especially depressive symptoms. These moods cannot be explained by stress or demographic factors.
http://dx.doi.org/10.1016/j.bbi.2012.07.053
http://dx.doi.org/10.1016/j.bbi.2012.07.055
30. Plasma oxytocin and vasopressin and social functioning J. Gouin a, C. Carter b, H. Pournajafi-Nazarloo b, R. Glaser c, W. Malarkey c, T. Loving c, J. Stowell c, J.K. Kiecolt-Glaser c
32. Lower morning cortisol is associated with depression, stress and lower IL-10 in dementia caregivers M. Rowe, M.W. Groer, J.W. Beckstead, B. Lehman
a
University of South Florida College of Nursing, 12910 Bruce B. Downs Blvd., Tampa, FL 33612, United States
Concordia University, Department of Psychology, 7141 Sherbrooke Street West, PY 170-14, Montréal, QC, Canada H4B 1R6 b University of Illinois at Chicago, United States c The Ohio State University, United States In animal studies, the neuropeptides oxytocin and vasopressin have been implicated in social behaviors. In humans, plasma levels of oxytocin covary with perceptions of relationship quality, but little is known about the association between plasma vasopressin and social behaviors in humans. The goal of this study was to evaluate the relationships among plasma oxytocin and vasopressin and selfreported social functioning. Thirty-seven couples completed measures of social functioning and provided blood samples for neuropeptide analysis during a 24-hour admission to a hospital-based research unit. Higher plasma oxytocin was associated with less hostility among men, p = .001, but not women, p = .67. Across both men and women greater levels of vasopressin were associated with larger social networks, p = .05, less negative spousal interactions, p = .03, less attachment avoidance, p = .03, more attachment security p = .04, and marginally with greater spousal social support, p = .06. Overall, higher social functioning was associated with greater plasma vasopressin levels. This study provides evidence that plasma vasopressin levels have small, but significant associations with dimensions of social functioning in humans.
Twenty-three caregivers of patients with dementia were followed in their home over several days. The sample was primarily female and White, Non-Hispanic with a mean age of 65.7 years. Morning (am) saliva samples were collected over two measurement days, and a blood sample was obtained. Cortisol was measured with ELISA. Blood was analyzed for C-reactive protein (CRP) and a 13-plex of cytokines. Instruments were the CES-D, the Perceived Stress scale (PSS), and the Pittsburgh Sleep Quality Index (PSQI). The PSS mean was 24.83, CES-D mean was 13.1, and Global PSQI was 8.6. A 13-plex of plasma cytokines was used for exploratory analysis using Millipore bead-based kits and a Luminex-200. CRP was measured by ELISA and the mean was 2.96 mg/L. Awakening salivary cortisol mean was 0.326 lg/dL. Only plasma Interleukin 10 (IL-10) was positively associated with awakening cortisol. Both stress and depression were inversely correlated with awakening cortisol. Poor sleep was related to stress and depression but to no biological variables. These data suggest that caregivers with higher stress and depression have lower awakening cortisol, and that lower awakening cortisol is associated with lower IL-10 levels. This may indicate disruption in the hypothalamic–pituitary–adrenal axis and a shift in an important regulatory cytokine, both of which could contribute to health effects in this vulnerable population.
http://dx.doi.org/10.1016/j.bbi.2012.07.054 http://dx.doi.org/10.1016/j.bbi.2012.07.056
31. Positive thyroid peroxidase antibody titer is associated with dysphoric moods during pregnancy and throughout the postpartum M. Groer, J.H. Vaughn, S.N. Williams University of South Florida College of Nursing, 12910 Bruce B. Downs Blvd., Tampa, FL 33647, United States Positive thyroid peroxidase antibody (TPO) titers during pregnancy predict development of autoimmune postpartum thyroiditis (PPT). Some studies have noted a relationship between TPO titers and postpartum depression. No studies have examined general dysphoric moods in TPO positive women during pregnancy and the postpartum. Pregnant women (N = 631) were screened for TPO antibodies. There were 63 euthyroid TPO positive women. A compar-
33. Programming of reproductive development by neonatal immunological challenge: Evidence for transgenerational inheritance L. Sominsky a, C.L. Meehan a, A.K. Walker b, L. Bobrovskaya c, E.A. McLaughlin d, D.M. Hodgson a a
Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle, Callaghan, NSW 2308, Australia b Integrative Immunology and Behavior Program, Department of Animal Sciences, Department of Medical Pathology, University of Illinois at Urbana-Champaign, Urbana, IL, United States c School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia d ARC Centre of Excellence in Biotechnology & Development, School of
S10
U. Püntener et al. / Brain, Behavior, and Immunity 26 (2012) S1–S50
Environmental & Life Sciences, Faculty of Science and IT, The University of Newcastle, Australia Neonatal immunological challenge produces long-term neuroendocrine, immune and behavioural alterations. Our findings indicate that exposure to lipopolysaccharide (LPS; 0.05 mg/kg, i.p.) on postnatal days (PNDs) 3 and 5 impairs sexual behaviour in rats, most notably in the female. Here we investigated the effect of neonatal LPS on female reproductive development. Developmental weight gain, puberty onset and oestrous cyclicity were monitored. Circulating HPA/ HPG hormones and ovarian morphology were examined throughout the development. Mating success and markers of reproductive development in the offspring were evaluated. Given the known involvement of the sympathetic nervous system in regulating ovarian maturation, tyrosine hydroxylase (TH) phosphorylation was assessed in neonatal adrenals. LPS exposure increased TH phosphorylation in neonatal adrenals (p < .01), increased corticosterone and reduced FSH levels (p < .05). LPS-treated females exhibited increased weight gain (p < .005), earlier puberty (p < .001), diminished ovarian reserve (p < .05) and advanced reproductive senescence (p < .05). LPS-treated dams produced larger litter-sizes, exhibiting higher mortality rates (p < .001). Their female offspring exhibited increased catch-up growth (p < .05), increased corticosterone (p < .01) and delayed puberty (p < .05). No such differences were observed in the male offspring. These results indicate a substantial effect of enhanced inflammatory responses experienced in early life on neuroendocrine development of the female rat, critical for sexual maturation and functioning. Importantly, altered development in the female, but not male offspring of LPS-treated mothers indicates a sexual dimorphism of neonatal immunological stress and its potential inheritance. http://dx.doi.org/10.1016/j.bbi.2012.07.057
34. Neonatal immune challenge induces anxiety in adulthood and is associated with functional alterations to the autonomic nervous system L. Sominsky a, E.A. Fuller a, E. Bondarenko b, L.K. Ong c, V.R. Clark d, L. Bobrovskaya e, P.R. Dunkley c, E. Nalivaiko b, D.M. Hodgson a a
Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle, Callaghan, NSW 2308, Australia b School of Biomedical Sciences & Pharmacy, The University of Newcastle, Australia c Medical Biochemistry, School of Biomedical Sciences & Pharmacy, The University of Newcastle, Australia d Human Biology, Brown University, United States e School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
behaviour (p < .05). The results suggest that in addition to the commonly reported changes in HPA axis functioning, neonatal LPS challenge produces a persistent change in ANS activity, associated with the anxiety-like phenotype described in many publications. The increased respiration evident in LPS-treated animals is also directly analogous to human anxiety patients whom show dysregulation of respiratory parameters during panic states. http://dx.doi.org/10.1016/j.bbi.2012.07.058
35. Grief is associated with cortisol awakening response and TNFalpha in female partners of veterans with traumatic brain injury K.L. Saban a,b, H.L. Mathews a, N.S. Hogan a, J.M. Griffin c, F.B. Bryant d, T.L. Pape b,e, E.G. Collins b,f, L. Witek Janusek a a Loyola University Chicago, 2160 S. First Ave., Maywood, IL 60565, United States b Edward Hines Jr. VA Hospital, United States c Minneapolis VA Health Care System, United States d Loyola University Chicago, United States e Northwestern Feinberg School of Medicine, United States f University of Illinois at Chicago, United States
Severe traumatic brain injury (TBI) produces permanent personality and cognitive changes. Grief, although traditionally conceptualized as a bereavement-related reaction, is also experienced by significant others in response to profound changes in their lovedone. Grief may be a key emotional process underlying neuroendocrine and inflammatory alterations among partners responding to changes in their loved-one following TBI. The purpose of this study was to determine whether grief is associated with alterations in cortisol awakening response (CAR) and levels of a proinflammatory cytokine (TNF-alpha) in partners of veterans with TBI. A cross-sectional sample of 40 women (mean age = 42 years) caring for a significant other who suffered a moderate or severe TBI from 6 months to 10 years ago were enrolled. Subjects completed the Perceived Stress Scale and Hogan Grief Reaction Checklist and provided saliva samples upon awakening and 30 min after awakening to measure CAR and TNF-alpha. Controlling for BMI and caregiving frequency and duration, CAR was inversely associated with perceived stress (r = .522, p = .007) and with the grief subscale of panic behavior (r = .489, p = .013). TNF-alpha was positively associated with grief subscales: detachment (r = .436, p = .030) and blame/anger (r = .480, p = .015). A blunted CAR may reflect ‘‘burnout’’ resulting from the chronic stress and grief experienced by caregivers. This may unleash proinflammatory cytokines and predispose caregivers to future inflammatory-related health risks. http://dx.doi.org/10.1016/j.bbi.2012.07.059
We have previously reported neonatal lipopolysaccharide (LPS; 0.05 mg/kg, i.p.) exposure produces robust increases in anxiety-like behaviour in rats in adulthood. An important physiological contributor to anxiety is considered to be sympathetic nervous system (SNS) and autonomic nervous system (ANS) activity. Here we report that neonatal LPS exposure results in immediate and persistent changes in SNS and ANS function. Programming of the ANS in Wistar rats neonatally treated with LPS was examined via assessment of tyrosine hydroxylase (TH) in neonatal and adult adrenals, and adult respiratory rate, using whole-body plethysmography assessed at baseline and in response to mild stress (acoustic and light stimuli). Anxiety-like behaviour was assessed in adulthood on the elevated plus maze (EPM) and holeboard. Neonatal LPS exposure produced an increase in TH phosphorylation and activity which persisted into adulthood (p < .05). In adulthood, LPS-treated rats responded with increased respiratory rate to the stimuli and exhibited elevated corticosterone following the testing (p < .05). These physiological changes were associated with significant increases in anxiety-like
36. Immune adaptation in the central nervous system in response to systemic infection U. Püntener, S.G. Booth, V.H. Perry, J.L. Teeling CNS Inflammation Group, Centre of Biological Sciences, University of Southampton, Southampton, United States Introduction: Acute systemic inflammation leads to production of inflammatory mediators and transient metabolic and behavioural changes. In models of chronic neurodegeneration this acute inflammation can cause neuronal damage through activation of ‘primed’ microglia. Here, we investigated innate immune activation in the healthy and diseased CNS in response to chronic systemic bacterial infection. Methods: Mice received a sublethal dose (10 6 pfu) of life Salmonella typhimurium. Serum, spleen and brain cytokines were mea-
S9
uptake inhibitor, 2 mg/kg-daily injections during 5 days post-lesion), on the expression of tyrosine hydroxylase (TH), GFAP (astrocyte marker), and OX-42 (microglia marker), evaluated by immunohistochemistry and/or immunoblotting in the substancia nigra (SN) of rat brains unilaterally injected with 6-hydroxy-dopamine. The ACEA group exhibited a decrease about 30% in the TH levels and an increase about 24% in the OX-42 expression in relation to the control group (treated with vehicle DMSO). The AM404 group presented a decrease about 10% in the expression of TH and an increase about 20% and 26% in the expression of GFAP and OX-42, respectively, compared with the DMSO group. Our results show, therefore, that the treatment with both cannabinoid compounds seems to promote an increase in the microglial activation in the SN and an increment of TH-neurons lost induced by the 6-hydroxy-dopamine. This study adds information about the role of cannabinoid system and cannabinoid compounds as possible therapeutic tools in PD. FAPESP and CNPq.
ison group of TPO negative women (N = 72) was randomly selected. All women were visited monthly for 6 months by a research nurse blinded to TPO status. A blood sample was obtained and a targeted physical exam was done. Women completed a thyroid symptom checklist, the Perceived Stress Scale and the Profile of Mood States. The blood was tested at each visit for thyroid stimulating hormone (TSH) levels for all TPO positive women and any TPO negative women with enlarged thyroid glands or positive symptoms. Pregnant TPO positive women had statistically significant higher depressive symptoms and more clinical depression than TPO negative women. There was significantly higher depression, anger, and total mood disturbance scores throughout the postpartum for TPO positive women compared to TPO negative women. This occurred regardless of development of PPT. The study suggests that TPO autoantibodies alone, in pregnant and postpartum women increases the possibility of negative dysphoric mood states, especially depressive symptoms. These moods cannot be explained by stress or demographic factors.
http://dx.doi.org/10.1016/j.bbi.2012.07.053
http://dx.doi.org/10.1016/j.bbi.2012.07.055
30. Plasma oxytocin and vasopressin and social functioning J. Gouin a, C. Carter b, H. Pournajafi-Nazarloo b, R. Glaser c, W. Malarkey c, T. Loving c, J. Stowell c, J.K. Kiecolt-Glaser c
32. Lower morning cortisol is associated with depression, stress and lower IL-10 in dementia caregivers M. Rowe, M.W. Groer, J.W. Beckstead, B. Lehman
a
University of South Florida College of Nursing, 12910 Bruce B. Downs Blvd., Tampa, FL 33612, United States
Concordia University, Department of Psychology, 7141 Sherbrooke Street West, PY 170-14, Montréal, QC, Canada H4B 1R6 b University of Illinois at Chicago, United States c The Ohio State University, United States In animal studies, the neuropeptides oxytocin and vasopressin have been implicated in social behaviors. In humans, plasma levels of oxytocin covary with perceptions of relationship quality, but little is known about the association between plasma vasopressin and social behaviors in humans. The goal of this study was to evaluate the relationships among plasma oxytocin and vasopressin and selfreported social functioning. Thirty-seven couples completed measures of social functioning and provided blood samples for neuropeptide analysis during a 24-hour admission to a hospital-based research unit. Higher plasma oxytocin was associated with less hostility among men, p = .001, but not women, p = .67. Across both men and women greater levels of vasopressin were associated with larger social networks, p = .05, less negative spousal interactions, p = .03, less attachment avoidance, p = .03, more attachment security p = .04, and marginally with greater spousal social support, p = .06. Overall, higher social functioning was associated with greater plasma vasopressin levels. This study provides evidence that plasma vasopressin levels have small, but significant associations with dimensions of social functioning in humans.
Twenty-three caregivers of patients with dementia were followed in their home over several days. The sample was primarily female and White, Non-Hispanic with a mean age of 65.7 years. Morning (am) saliva samples were collected over two measurement days, and a blood sample was obtained. Cortisol was measured with ELISA. Blood was analyzed for C-reactive protein (CRP) and a 13-plex of cytokines. Instruments were the CES-D, the Perceived Stress scale (PSS), and the Pittsburgh Sleep Quality Index (PSQI). The PSS mean was 24.83, CES-D mean was 13.1, and Global PSQI was 8.6. A 13-plex of plasma cytokines was used for exploratory analysis using Millipore bead-based kits and a Luminex-200. CRP was measured by ELISA and the mean was 2.96 mg/L. Awakening salivary cortisol mean was 0.326 lg/dL. Only plasma Interleukin 10 (IL-10) was positively associated with awakening cortisol. Both stress and depression were inversely correlated with awakening cortisol. Poor sleep was related to stress and depression but to no biological variables. These data suggest that caregivers with higher stress and depression have lower awakening cortisol, and that lower awakening cortisol is associated with lower IL-10 levels. This may indicate disruption in the hypothalamic–pituitary–adrenal axis and a shift in an important regulatory cytokine, both of which could contribute to health effects in this vulnerable population.
http://dx.doi.org/10.1016/j.bbi.2012.07.054 http://dx.doi.org/10.1016/j.bbi.2012.07.056
31. Positive thyroid peroxidase antibody titer is associated with dysphoric moods during pregnancy and throughout the postpartum M. Groer, J.H. Vaughn, S.N. Williams University of South Florida College of Nursing, 12910 Bruce B. Downs Blvd., Tampa, FL 33647, United States Positive thyroid peroxidase antibody (TPO) titers during pregnancy predict development of autoimmune postpartum thyroiditis (PPT). Some studies have noted a relationship between TPO titers and postpartum depression. No studies have examined general dysphoric moods in TPO positive women during pregnancy and the postpartum. Pregnant women (N = 631) were screened for TPO antibodies. There were 63 euthyroid TPO positive women. A compar-
33. Programming of reproductive development by neonatal immunological challenge: Evidence for transgenerational inheritance L. Sominsky a, C.L. Meehan a, A.K. Walker b, L. Bobrovskaya c, E.A. McLaughlin d, D.M. Hodgson a a
Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle, Callaghan, NSW 2308, Australia b Integrative Immunology and Behavior Program, Department of Animal Sciences, Department of Medical Pathology, University of Illinois at Urbana-Champaign, Urbana, IL, United States c School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia d ARC Centre of Excellence in Biotechnology & Development, School of
S10
U. Püntener et al. / Brain, Behavior, and Immunity 26 (2012) S1–S50
Environmental & Life Sciences, Faculty of Science and IT, The University of Newcastle, Australia Neonatal immunological challenge produces long-term neuroendocrine, immune and behavioural alterations. Our findings indicate that exposure to lipopolysaccharide (LPS; 0.05 mg/kg, i.p.) on postnatal days (PNDs) 3 and 5 impairs sexual behaviour in rats, most notably in the female. Here we investigated the effect of neonatal LPS on female reproductive development. Developmental weight gain, puberty onset and oestrous cyclicity were monitored. Circulating HPA/ HPG hormones and ovarian morphology were examined throughout the development. Mating success and markers of reproductive development in the offspring were evaluated. Given the known involvement of the sympathetic nervous system in regulating ovarian maturation, tyrosine hydroxylase (TH) phosphorylation was assessed in neonatal adrenals. LPS exposure increased TH phosphorylation in neonatal adrenals (p < .01), increased corticosterone and reduced FSH levels (p < .05). LPS-treated females exhibited increased weight gain (p < .005), earlier puberty (p < .001), diminished ovarian reserve (p < .05) and advanced reproductive senescence (p < .05). LPS-treated dams produced larger litter-sizes, exhibiting higher mortality rates (p < .001). Their female offspring exhibited increased catch-up growth (p < .05), increased corticosterone (p < .01) and delayed puberty (p < .05). No such differences were observed in the male offspring. These results indicate a substantial effect of enhanced inflammatory responses experienced in early life on neuroendocrine development of the female rat, critical for sexual maturation and functioning. Importantly, altered development in the female, but not male offspring of LPS-treated mothers indicates a sexual dimorphism of neonatal immunological stress and its potential inheritance. http://dx.doi.org/10.1016/j.bbi.2012.07.057
34. Neonatal immune challenge induces anxiety in adulthood and is associated with functional alterations to the autonomic nervous system L. Sominsky a, E.A. Fuller a, E. Bondarenko b, L.K. Ong c, V.R. Clark d, L. Bobrovskaya e, P.R. Dunkley c, E. Nalivaiko b, D.M. Hodgson a a
Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle, Callaghan, NSW 2308, Australia b School of Biomedical Sciences & Pharmacy, The University of Newcastle, Australia c Medical Biochemistry, School of Biomedical Sciences & Pharmacy, The University of Newcastle, Australia d Human Biology, Brown University, United States e School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
behaviour (p < .05). The results suggest that in addition to the commonly reported changes in HPA axis functioning, neonatal LPS challenge produces a persistent change in ANS activity, associated with the anxiety-like phenotype described in many publications. The increased respiration evident in LPS-treated animals is also directly analogous to human anxiety patients whom show dysregulation of respiratory parameters during panic states. http://dx.doi.org/10.1016/j.bbi.2012.07.058
35. Grief is associated with cortisol awakening response and TNFalpha in female partners of veterans with traumatic brain injury K.L. Saban a,b, H.L. Mathews a, N.S. Hogan a, J.M. Griffin c, F.B. Bryant d, T.L. Pape b,e, E.G. Collins b,f, L. Witek Janusek a a Loyola University Chicago, 2160 S. First Ave., Maywood, IL 60565, United States b Edward Hines Jr. VA Hospital, United States c Minneapolis VA Health Care System, United States d Loyola University Chicago, United States e Northwestern Feinberg School of Medicine, United States f University of Illinois at Chicago, United States
Severe traumatic brain injury (TBI) produces permanent personality and cognitive changes. Grief, although traditionally conceptualized as a bereavement-related reaction, is also experienced by significant others in response to profound changes in their lovedone. Grief may be a key emotional process underlying neuroendocrine and inflammatory alterations among partners responding to changes in their loved-one following TBI. The purpose of this study was to determine whether grief is associated with alterations in cortisol awakening response (CAR) and levels of a proinflammatory cytokine (TNF-alpha) in partners of veterans with TBI. A cross-sectional sample of 40 women (mean age = 42 years) caring for a significant other who suffered a moderate or severe TBI from 6 months to 10 years ago were enrolled. Subjects completed the Perceived Stress Scale and Hogan Grief Reaction Checklist and provided saliva samples upon awakening and 30 min after awakening to measure CAR and TNF-alpha. Controlling for BMI and caregiving frequency and duration, CAR was inversely associated with perceived stress (r = .522, p = .007) and with the grief subscale of panic behavior (r = .489, p = .013). TNF-alpha was positively associated with grief subscales: detachment (r = .436, p = .030) and blame/anger (r = .480, p = .015). A blunted CAR may reflect ‘‘burnout’’ resulting from the chronic stress and grief experienced by caregivers. This may unleash proinflammatory cytokines and predispose caregivers to future inflammatory-related health risks. http://dx.doi.org/10.1016/j.bbi.2012.07.059
We have previously reported neonatal lipopolysaccharide (LPS; 0.05 mg/kg, i.p.) exposure produces robust increases in anxiety-like behaviour in rats in adulthood. An important physiological contributor to anxiety is considered to be sympathetic nervous system (SNS) and autonomic nervous system (ANS) activity. Here we report that neonatal LPS exposure results in immediate and persistent changes in SNS and ANS function. Programming of the ANS in Wistar rats neonatally treated with LPS was examined via assessment of tyrosine hydroxylase (TH) in neonatal and adult adrenals, and adult respiratory rate, using whole-body plethysmography assessed at baseline and in response to mild stress (acoustic and light stimuli). Anxiety-like behaviour was assessed in adulthood on the elevated plus maze (EPM) and holeboard. Neonatal LPS exposure produced an increase in TH phosphorylation and activity which persisted into adulthood (p < .05). In adulthood, LPS-treated rats responded with increased respiratory rate to the stimuli and exhibited elevated corticosterone following the testing (p < .05). These physiological changes were associated with significant increases in anxiety-like
36. Immune adaptation in the central nervous system in response to systemic infection U. Püntener, S.G. Booth, V.H. Perry, J.L. Teeling CNS Inflammation Group, Centre of Biological Sciences, University of Southampton, Southampton, United States Introduction: Acute systemic inflammation leads to production of inflammatory mediators and transient metabolic and behavioural changes. In models of chronic neurodegeneration this acute inflammation can cause neuronal damage through activation of ‘primed’ microglia. Here, we investigated innate immune activation in the healthy and diseased CNS in response to chronic systemic bacterial infection. Methods: Mice received a sublethal dose (10 6 pfu) of life Salmonella typhimurium. Serum, spleen and brain cytokines were mea-