- Email: [email protected]
160. Acute exercise preferentially mobilizes NK-cells with a late-differentiated phenotype
V.A. Peters et al. / Brain, Behavior, and Immunity 26 (2012) S1–S50
alterations in microglia activation contribute to age-related reductions in hippocampal neurogenesis. http://dx.doi.org/10.1016/j.bbi.2012.07.183
160. Acute exercise preferentially mobilizes NK-cells with a latedifferentiated phenotype A.B. Bigley a, E.P. Lavoy a, M. Momcilovic a, J. Reed a, T. Ograjsek b, R.J. Simpson a,b a
University of Houston, Department of Health and Human Performance, 3855 Holman St., Houston, TX 77204-6015, United States b Edinburgh Napier University, UK
NK-cells undergo an ‘‘education’’ process as they develop into fully-functional cells capable of efficiently killing targets. As NK-cells mature, they express more inhibitory-KIR and inhibitory-KIR expression is positively associated with NK-cell function. NK-cells with insufficient inhibitory-KIR/MHC I or excessive activating-KIR/MHC I interactions become anergic. As with CD8+ T-cells, trafficking of late-differentiated NK-cells with high cytotoxicity to the periphery may play a role in the acute response to exercise. In this study, participants performed 30-min of cycling exercise at 95%, 105%, and 115% of lactate-threshold with blood collections taken before, immediately-after, and 1-h-after exercise. Whole blood flow cytometry was performed to determine cell counts and phenotype. CD158a+/ NKG2A late-differentiated NK-cells were preferentially mobilized into the blood immediately after exercise relative to CD158a+/ NKG2A+ intermediate- or CD158a /NKG2A+ early-differentiated NK-cells (322% vs. 223% and 212%, p < 0.01). Similarly, CD158b+/ NKG2A NK-cells are mobilized more than CD158b+/NKG2A+ or CD158b /NKG2A+ NK-cells (332% vs. 253% and 226%, p < 0.01), and CD158e+/NKG2A NK-cells are mobilized more than CD158e+/ NKG2A+ or CD158e /NKG2A+ NK-cells (319% vs. 248% and 219%, p < 0.05). NK-cells expressing the activating-KIR NKG2C were mobilized less than NKG2C NK-cells (191% vs. 328%, p < 0.001) and NKcells expressing the terminal-differentiation marker CD57 were mobilized more than CD57- NK-cells (325% vs. 222%, p < 0.01). These data suggest that late-differentiated NK-cells are preferentially mobilized into the blood following acute aerobic exercise. Trafficking of NK-cells with greater cytotoxicity may facilitate clearance of exercise-damaged cells. http://dx.doi.org/10.1016/j.bbi.2012.07.184
161. Inhibition of indoleamine 2,3-dioxygenase prevents amyloid-beta-induced neuropsychiatric-like behaviors in mice J.M. Parrott a,b, A. Salazar a, L. Redus a, A. Green a, C.T. Skalomenos a, J.M. Heisler a,b, J.C. O’Connor a,b a
Department of Pharmacology, School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States b Center for Biomedical Neurosciences, San Antonio, TX, United States Neuropsychiatric disorders, such as depression and anxiety are the most prevalent comorbidities of Alzheimer’s disease (AD), accelerating cognitive decline and impairing quality-of-life. Post-mortem analysis of brain tissue from AD patients has revealed increased proinflammatory cytokines, indicative of chronic neuroimmune activation, possibly due to AD-related pathology. Recent data has shown that activation of the immune system can precipitate neuropsychiatric symptoms, which may be mediated through the tryptophan metabolizing enzyme, indoleamine 2,3-dioxygenase (IDO). We sought to determine if central amyloid-beta (1–42) administration caused neuroimmune activation and subsequent IDO-dependent
S45
neuropsychiatric-like behaviors. Male C57BL/J6 mice received a single intracerebroventricular injection of amyloid-beta (1–42) (400 pmol/1lL) or vehicle. Sucrose preference was measured 3 days post-injection, while open field activity and behavior during the forced swim test were measured 7 days post-injections. Amyloidbeta (1–42) or vehicle was also administered to IDO deficient mice (IDO / ) or mice pretreated with a competitive IDO inhibitor (1methyltryptophan, 1-MT). In control mice, amyloid-beta (1–42) administration triggered an increase in depressive- and anxiety-like behaviors, characterized by a reduction in sucrose preference, decreased open field central time, increased open field thigmotaxis, and increased immobility during the forced swim test. These neuropsychiatric-like behaviors did not develop in response to amyloidbeta (1–42) administration after 1-MT pretreatment or in IDO / mice. Together, these data suggest IDO may play an important role in mediating AD-related neuropsychiatric disorders. http://dx.doi.org/10.1016/j.bbi.2012.07.185
162. Comorbid chronic pain and depression: A search for common neuroimmune mechanisms W. Zhou a, R. Dantzer b, K.W. Kelley a, A. Kavelaars a a Integrative Immunology and Behavior Program, University of Illinois Urbana Champaign, 1201 W. Gregory Drive, Urbana, IL 61801, United States b Department of Symptoms Research, MD Anderson Cancer Center, Houston, TX, United States
In humans, chronic neuropathic pain is a risk factor for depression, but the mechanisms underlying this association remain elusive. Spared nerve injury (SNI) is a rodent model of chronic neuropathic pain that is associated with depressive-like behavior in most studies. Central nervous system microglial activation and pro-inflammatory cytokine production contribute to both chronic neuropathic pain and depressive-like after SNI. We have recently established that depressive-like behavior induced by peripheral inflammation requires the activation of IDO-1, a tryptophan metabolizing enzyme. Here we determined the contribution of IDO-1 to SNI-induced neuropathic pain and depressive-like behavior. SNI or sham surgery was performed in wild type and IDO-1-KO mice. As expected, SNI induced the development of mechanical hyperalgesia as well as depressive-like behavior (reduced sucrose preference and increased immobility in the forced swim test), without affecting locomotor activity in a novel cage. In accordance with results from others, SNI increased brain pro-inflammatory cytokine production. IDO-1KO mice developed mechanical hyperalgesia with similar kinetics and severity as WT mice. However, IDO-1 KO mice did not develop depressive-like behavior. In conclusion, IDO-1 is a critical enzyme required for development of depressive-like behavior in the context of neuropathic pain after SNI. The involvement of IDO-1 in depression is specific since its absence does not modify the pain response after SNI. Funded by NIH R01-NS073939 (A.K., R.D., K.W.K.); RO1NS074999 (A.K.); R01-MH079829 (R.D.), R01-AG-029573 (K.W.K.). http://dx.doi.org/10.1016/j.bbi.2012.07.186
163. Macrophages up-regulate IL-1 receptor type 2 (IL-1R2) gene expression during acute hypoxia V.A. Peters, D.D. Meling, K.A. Kwakwa, G.G. Freund University of Illinois at Urbana-Champaign, 1201 W. Gregory Ave., Urbana, IL 61801, United States IL-1R2 is a critical regulator of IL-1 bioaction but its role in acute hypoxia is not clear. Here we examine its expression during acute
alterations in microglia activation contribute to age-related reductions in hippocampal neurogenesis. http://dx.doi.org/10.1016/j.bbi.2012.07.183
160. Acute exercise preferentially mobilizes NK-cells with a latedifferentiated phenotype A.B. Bigley a, E.P. Lavoy a, M. Momcilovic a, J. Reed a, T. Ograjsek b, R.J. Simpson a,b a
University of Houston, Department of Health and Human Performance, 3855 Holman St., Houston, TX 77204-6015, United States b Edinburgh Napier University, UK
NK-cells undergo an ‘‘education’’ process as they develop into fully-functional cells capable of efficiently killing targets. As NK-cells mature, they express more inhibitory-KIR and inhibitory-KIR expression is positively associated with NK-cell function. NK-cells with insufficient inhibitory-KIR/MHC I or excessive activating-KIR/MHC I interactions become anergic. As with CD8+ T-cells, trafficking of late-differentiated NK-cells with high cytotoxicity to the periphery may play a role in the acute response to exercise. In this study, participants performed 30-min of cycling exercise at 95%, 105%, and 115% of lactate-threshold with blood collections taken before, immediately-after, and 1-h-after exercise. Whole blood flow cytometry was performed to determine cell counts and phenotype. CD158a+/ NKG2A late-differentiated NK-cells were preferentially mobilized into the blood immediately after exercise relative to CD158a+/ NKG2A+ intermediate- or CD158a /NKG2A+ early-differentiated NK-cells (322% vs. 223% and 212%, p < 0.01). Similarly, CD158b+/ NKG2A NK-cells are mobilized more than CD158b+/NKG2A+ or CD158b /NKG2A+ NK-cells (332% vs. 253% and 226%, p < 0.01), and CD158e+/NKG2A NK-cells are mobilized more than CD158e+/ NKG2A+ or CD158e /NKG2A+ NK-cells (319% vs. 248% and 219%, p < 0.05). NK-cells expressing the activating-KIR NKG2C were mobilized less than NKG2C NK-cells (191% vs. 328%, p < 0.001) and NKcells expressing the terminal-differentiation marker CD57 were mobilized more than CD57- NK-cells (325% vs. 222%, p < 0.01). These data suggest that late-differentiated NK-cells are preferentially mobilized into the blood following acute aerobic exercise. Trafficking of NK-cells with greater cytotoxicity may facilitate clearance of exercise-damaged cells. http://dx.doi.org/10.1016/j.bbi.2012.07.184
161. Inhibition of indoleamine 2,3-dioxygenase prevents amyloid-beta-induced neuropsychiatric-like behaviors in mice J.M. Parrott a,b, A. Salazar a, L. Redus a, A. Green a, C.T. Skalomenos a, J.M. Heisler a,b, J.C. O’Connor a,b a
Department of Pharmacology, School of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States b Center for Biomedical Neurosciences, San Antonio, TX, United States Neuropsychiatric disorders, such as depression and anxiety are the most prevalent comorbidities of Alzheimer’s disease (AD), accelerating cognitive decline and impairing quality-of-life. Post-mortem analysis of brain tissue from AD patients has revealed increased proinflammatory cytokines, indicative of chronic neuroimmune activation, possibly due to AD-related pathology. Recent data has shown that activation of the immune system can precipitate neuropsychiatric symptoms, which may be mediated through the tryptophan metabolizing enzyme, indoleamine 2,3-dioxygenase (IDO). We sought to determine if central amyloid-beta (1–42) administration caused neuroimmune activation and subsequent IDO-dependent
S45
neuropsychiatric-like behaviors. Male C57BL/J6 mice received a single intracerebroventricular injection of amyloid-beta (1–42) (400 pmol/1lL) or vehicle. Sucrose preference was measured 3 days post-injection, while open field activity and behavior during the forced swim test were measured 7 days post-injections. Amyloidbeta (1–42) or vehicle was also administered to IDO deficient mice (IDO / ) or mice pretreated with a competitive IDO inhibitor (1methyltryptophan, 1-MT). In control mice, amyloid-beta (1–42) administration triggered an increase in depressive- and anxiety-like behaviors, characterized by a reduction in sucrose preference, decreased open field central time, increased open field thigmotaxis, and increased immobility during the forced swim test. These neuropsychiatric-like behaviors did not develop in response to amyloidbeta (1–42) administration after 1-MT pretreatment or in IDO / mice. Together, these data suggest IDO may play an important role in mediating AD-related neuropsychiatric disorders. http://dx.doi.org/10.1016/j.bbi.2012.07.185
162. Comorbid chronic pain and depression: A search for common neuroimmune mechanisms W. Zhou a, R. Dantzer b, K.W. Kelley a, A. Kavelaars a a Integrative Immunology and Behavior Program, University of Illinois Urbana Champaign, 1201 W. Gregory Drive, Urbana, IL 61801, United States b Department of Symptoms Research, MD Anderson Cancer Center, Houston, TX, United States
In humans, chronic neuropathic pain is a risk factor for depression, but the mechanisms underlying this association remain elusive. Spared nerve injury (SNI) is a rodent model of chronic neuropathic pain that is associated with depressive-like behavior in most studies. Central nervous system microglial activation and pro-inflammatory cytokine production contribute to both chronic neuropathic pain and depressive-like after SNI. We have recently established that depressive-like behavior induced by peripheral inflammation requires the activation of IDO-1, a tryptophan metabolizing enzyme. Here we determined the contribution of IDO-1 to SNI-induced neuropathic pain and depressive-like behavior. SNI or sham surgery was performed in wild type and IDO-1-KO mice. As expected, SNI induced the development of mechanical hyperalgesia as well as depressive-like behavior (reduced sucrose preference and increased immobility in the forced swim test), without affecting locomotor activity in a novel cage. In accordance with results from others, SNI increased brain pro-inflammatory cytokine production. IDO-1KO mice developed mechanical hyperalgesia with similar kinetics and severity as WT mice. However, IDO-1 KO mice did not develop depressive-like behavior. In conclusion, IDO-1 is a critical enzyme required for development of depressive-like behavior in the context of neuropathic pain after SNI. The involvement of IDO-1 in depression is specific since its absence does not modify the pain response after SNI. Funded by NIH R01-NS073939 (A.K., R.D., K.W.K.); RO1NS074999 (A.K.); R01-MH079829 (R.D.), R01-AG-029573 (K.W.K.). http://dx.doi.org/10.1016/j.bbi.2012.07.186
163. Macrophages up-regulate IL-1 receptor type 2 (IL-1R2) gene expression during acute hypoxia V.A. Peters, D.D. Meling, K.A. Kwakwa, G.G. Freund University of Illinois at Urbana-Champaign, 1201 W. Gregory Ave., Urbana, IL 61801, United States IL-1R2 is a critical regulator of IL-1 bioaction but its role in acute hypoxia is not clear. Here we examine its expression during acute