- Email: [email protected]
72. Immunohistochemical demonstration of enhanced prostaglandin F2alpha production following kainic acid-induced seizures in rat hippocampus
Abstracts / Brain, Behavior, and Immunity 32 (2013) e1–e47
cyte-linked behavioural disturbances may not due to a loss of cells but rather due to significant remodelling of the astrocyte network. http://dx.doi.org/10.1016/j.bbi.2013.07.082
71. Surprise, surprise: Glucocorticoids have a minor role compared to catecholamines and prostaglandins in mediating stress and surgery-induced In vivo suppression of NK activity S. Ben-Eliyahu, E. Rosenne, L. Sorski, L. Shaashua, E. Neeman, P. Matzner, B. Levi, N. Gotlieb
e21
mined in this pathological condition. Here we investigated the tissue distribution of PGF2alpha in the rat hippocampus during the acute phase of KA-induced exitotoxic injury using a novel immunostaining method. We devised a method to stain PGF2alpha using systemic perfusion fixation with water-soluble carbodiimide fixative, followed by immunofluorescence staining with anti-PGF2alpha antibody. Clearly detectable immunolabeling for PGF2alpha was chiefly evident in hippocampal neurons of the CA3 sector in KA-treated rats. PGF2alpha-immunopositive neurons also expressed cytosolic phospholipases A2, COX-2 and FP receptor. These results suggest that hippocampal neuronal PGF2alpha may play a pathophysiological role in an autocrine/paracrine manner during status epilepticus.
Tel Aviv University, Psychology, P.O. Box 39040, Tel Aviv 69978, Israel In vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, these findings are insufficient to conclude regarding the impact of endogenous release of these factors on in vivolevels of NKCC. Here we used an in vivo approach that sensitively and specifically reflects NKCC in living F344 rats, based on lung clearance of NK-sensitive tumor cells (MADB106), and based on comparing effects between NK-intact and NK-depleted rats. To this end we administered corticosterone, epinephrine, or prostaglandins to rats, or antagonized their endogenous release following different stress paradigms or surgery. The results indicated that corticosterone can modulate in vivo levels of NKCC only under some conditions, and mostly secondarily to the NK-suppressing impact of epinephrine. Specifically, corticosterone-induced NKCC suppression occurred (i) only under prolonged, but not short exposure to stress, and mainly in males; (ii) was smaller than the prominent impact of epinephrine; (iii) was mostly ascribed to corticosterone-induced potentiation of the effects of epinephrine and/or prostaglandins; and (iv) was completely abolished through antagonizing epinephrine and/or prostaglandins. Overall, these findings markedly limit the significance of stress/surgery-induced corticosterone release in the in vivo suppression of NKCC, and highlight the blockade of epinephrine and/or prostaglandins as effective and clinically feasible approaches to overcome such NK immuno-suppressive effects. http://dx.doi.org/10.1016/j.bbi.2013.07.083
72. Immunohistochemical demonstration of enhanced prostaglandin F2alpha production following kainic acid-induced seizures in rat hippocampus S. Takei a,b, S. Hasegawa-Ishii a,c, D.F. Woodward d, K. Watanabe b, A. Shimada a,e a
Dept. of Pathology, Inst. for Developmental Research, Aichi Human Service Center, 713-8 Kamiya Cho, Kasugai, Aichi, 480-0392, Japan b Dept. of Nutrition, Koshien University, Takarazuka, Japan c Research Fellow of the Japan Society for the Promotion of Science, Japan d Dept. of Biological Sciences, Allergan, Inc., USA e Dept. of Pathology, Laboratory Medicine and Radiologic Technology, Central Hospital, Aichi Human Service Center, Japan Prostaglandin (PG) F2alpha is one of the major prostanoids biosynthesized from arachidonic acid and catalyzed by cyclooxygenases (COXs). PGF2alpha exerts various biological functions by binding to the FP receptor. We previously demonstrated a pathological role for a surge in the production of PGF2alpha and other prostanoids during kainic acid (KA)-induced status epilepticus in subsequent chronic progressive hippocampal neuronal death. However, the precise distribution of hippocampal prostanoids remained to be deter-
http://dx.doi.org/10.1016/j.bbi.2013.07.084
73. Neurobehavioral consequences of acute mTOR inhibition M. Hadamitzky a, A. Herring b, K. Keyvani b, R. Doenlen c, H. Engler a, U. Krügel d, K. Bösche a, K. Orlowski a, M. Schedlowski a a Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, Germany b Institute of Pathology and Neuropathology, University Hospital Essen, Essen, Germany c Laboratory of Psychology and Behavioral Immunobiology, ETH Zurich, Switzerland d Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany
Evidence exists that immunotherapy with cytokines (e.g. interferon-alpha, interleukin-2) or calcineurin inhibitors (e.g. cyclosporin A) is accompanied by neuropsychiatric side effects, such as depressive symptoms, major depression or anxiety. Even though studies documented favorable psychiatric outcomes during immunosuppression using mammalian target of rapamycin (mTOR) inhibitiors, post mortem studies in subjects diagosed with major depressive disorders (MDD) revealed robust deficits in mTOR signaling in the prefrontal cortex. mTOR is a member of the phosphatidyl inositol 3kinase family (PI3K) and as a multifunctional serine–threonine kinase it acts as central regulator of cell growth, proliferation, and apoptosis. The present study investigated in rats possible neurobehavioral consequences of mTOR inhibition after single systemic administration of the immunosuppressive compound rapamycin (RAPA). Our data demonstrate that acute RAPA treatment (3 mg/kg i.p.) led to a significant increase in neuronal activity and elevated expression of FOS protein level in the amygdala, a brain structure critically involved in the modulation of mood and cognitive functions. Moreover, these neuronal amygdaloid changes were accompanied by enhanced anxiety-like behavior assessed in the elevated plus-maze and the open field test. Our findings indicate that acute immunosuppression due to mTOR inhibition with RAPA may raise the incidence rate to develop neurobehavioral complications. Weather and to what extend such effects arise during long-term immunotherapy using mTOR inhibition remains to be investigated. http://dx.doi.org/10.1016/j.bbi.2013.07.085
74. Recent stressful events contribute to the development of fatigue and depression in patients receiving Interferon-a treatment A. Borsini, N. Hepgul, V. Mondelli, T. Chalder, C. Pariante Department of Psychological Medicine, Institute of Psychiatry, King’s College London, 125 Coldharbour Lane, London SE5 9NU, United Kingdom
cyte-linked behavioural disturbances may not due to a loss of cells but rather due to significant remodelling of the astrocyte network. http://dx.doi.org/10.1016/j.bbi.2013.07.082
71. Surprise, surprise: Glucocorticoids have a minor role compared to catecholamines and prostaglandins in mediating stress and surgery-induced In vivo suppression of NK activity S. Ben-Eliyahu, E. Rosenne, L. Sorski, L. Shaashua, E. Neeman, P. Matzner, B. Levi, N. Gotlieb
e21
mined in this pathological condition. Here we investigated the tissue distribution of PGF2alpha in the rat hippocampus during the acute phase of KA-induced exitotoxic injury using a novel immunostaining method. We devised a method to stain PGF2alpha using systemic perfusion fixation with water-soluble carbodiimide fixative, followed by immunofluorescence staining with anti-PGF2alpha antibody. Clearly detectable immunolabeling for PGF2alpha was chiefly evident in hippocampal neurons of the CA3 sector in KA-treated rats. PGF2alpha-immunopositive neurons also expressed cytosolic phospholipases A2, COX-2 and FP receptor. These results suggest that hippocampal neuronal PGF2alpha may play a pathophysiological role in an autocrine/paracrine manner during status epilepticus.
Tel Aviv University, Psychology, P.O. Box 39040, Tel Aviv 69978, Israel In vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, these findings are insufficient to conclude regarding the impact of endogenous release of these factors on in vivolevels of NKCC. Here we used an in vivo approach that sensitively and specifically reflects NKCC in living F344 rats, based on lung clearance of NK-sensitive tumor cells (MADB106), and based on comparing effects between NK-intact and NK-depleted rats. To this end we administered corticosterone, epinephrine, or prostaglandins to rats, or antagonized their endogenous release following different stress paradigms or surgery. The results indicated that corticosterone can modulate in vivo levels of NKCC only under some conditions, and mostly secondarily to the NK-suppressing impact of epinephrine. Specifically, corticosterone-induced NKCC suppression occurred (i) only under prolonged, but not short exposure to stress, and mainly in males; (ii) was smaller than the prominent impact of epinephrine; (iii) was mostly ascribed to corticosterone-induced potentiation of the effects of epinephrine and/or prostaglandins; and (iv) was completely abolished through antagonizing epinephrine and/or prostaglandins. Overall, these findings markedly limit the significance of stress/surgery-induced corticosterone release in the in vivo suppression of NKCC, and highlight the blockade of epinephrine and/or prostaglandins as effective and clinically feasible approaches to overcome such NK immuno-suppressive effects. http://dx.doi.org/10.1016/j.bbi.2013.07.083
72. Immunohistochemical demonstration of enhanced prostaglandin F2alpha production following kainic acid-induced seizures in rat hippocampus S. Takei a,b, S. Hasegawa-Ishii a,c, D.F. Woodward d, K. Watanabe b, A. Shimada a,e a
Dept. of Pathology, Inst. for Developmental Research, Aichi Human Service Center, 713-8 Kamiya Cho, Kasugai, Aichi, 480-0392, Japan b Dept. of Nutrition, Koshien University, Takarazuka, Japan c Research Fellow of the Japan Society for the Promotion of Science, Japan d Dept. of Biological Sciences, Allergan, Inc., USA e Dept. of Pathology, Laboratory Medicine and Radiologic Technology, Central Hospital, Aichi Human Service Center, Japan Prostaglandin (PG) F2alpha is one of the major prostanoids biosynthesized from arachidonic acid and catalyzed by cyclooxygenases (COXs). PGF2alpha exerts various biological functions by binding to the FP receptor. We previously demonstrated a pathological role for a surge in the production of PGF2alpha and other prostanoids during kainic acid (KA)-induced status epilepticus in subsequent chronic progressive hippocampal neuronal death. However, the precise distribution of hippocampal prostanoids remained to be deter-
http://dx.doi.org/10.1016/j.bbi.2013.07.084
73. Neurobehavioral consequences of acute mTOR inhibition M. Hadamitzky a, A. Herring b, K. Keyvani b, R. Doenlen c, H. Engler a, U. Krügel d, K. Bösche a, K. Orlowski a, M. Schedlowski a a Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, Germany b Institute of Pathology and Neuropathology, University Hospital Essen, Essen, Germany c Laboratory of Psychology and Behavioral Immunobiology, ETH Zurich, Switzerland d Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany
Evidence exists that immunotherapy with cytokines (e.g. interferon-alpha, interleukin-2) or calcineurin inhibitors (e.g. cyclosporin A) is accompanied by neuropsychiatric side effects, such as depressive symptoms, major depression or anxiety. Even though studies documented favorable psychiatric outcomes during immunosuppression using mammalian target of rapamycin (mTOR) inhibitiors, post mortem studies in subjects diagosed with major depressive disorders (MDD) revealed robust deficits in mTOR signaling in the prefrontal cortex. mTOR is a member of the phosphatidyl inositol 3kinase family (PI3K) and as a multifunctional serine–threonine kinase it acts as central regulator of cell growth, proliferation, and apoptosis. The present study investigated in rats possible neurobehavioral consequences of mTOR inhibition after single systemic administration of the immunosuppressive compound rapamycin (RAPA). Our data demonstrate that acute RAPA treatment (3 mg/kg i.p.) led to a significant increase in neuronal activity and elevated expression of FOS protein level in the amygdala, a brain structure critically involved in the modulation of mood and cognitive functions. Moreover, these neuronal amygdaloid changes were accompanied by enhanced anxiety-like behavior assessed in the elevated plus-maze and the open field test. Our findings indicate that acute immunosuppression due to mTOR inhibition with RAPA may raise the incidence rate to develop neurobehavioral complications. Weather and to what extend such effects arise during long-term immunotherapy using mTOR inhibition remains to be investigated. http://dx.doi.org/10.1016/j.bbi.2013.07.085
74. Recent stressful events contribute to the development of fatigue and depression in patients receiving Interferon-a treatment A. Borsini, N. Hepgul, V. Mondelli, T. Chalder, C. Pariante Department of Psychological Medicine, Institute of Psychiatry, King’s College London, 125 Coldharbour Lane, London SE5 9NU, United Kingdom