18 results on '"J. Bredehöft"'
Search Results
2. Visualizing and profiling lipids in the OVLT of Fat-1 and wild type mouse brains during LPS-induced systemic inflammation using AP-SMALDI MSI
- Author
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Joachim Roth, Bernhard Spengler, Sophie Layé, Christoph Rummel, Fabian Johannes Pflieger, Sabine Schulz, Rüdiger Gerstberger, J. Bredehöft, Jing X. Kang, Konstantin Mayer, Dhaka Ram Bhandari, Justus-Liebig-Universität Gießen (JLU), Institute of Inorganic and Analytical Chemistry, Harvard Medical School [Boston] (HMS), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, and University Hospital of Giessen and Marburg (UKGM)
- Subjects
Lipopolysaccharides ,Male ,Genetically modified mouse ,Lipopolysaccharide ,Physiology ,MALDI imaging ,Cognitive Neuroscience ,[SDV]Life Sciences [q-bio] ,Mice, Transgenic ,Inflammation ,Systemic inflammation ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Organum Vasculosum ,Vascular organ of laminae terminalis ,030304 developmental biology ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Lamina terminalis ,Omega-3 polyunsaturated fatty acids ,Wild type ,Lipid metabolism ,Cell Biology ,General Medicine ,Cadherins ,Lipid Metabolism ,Lipids ,Molecular biology ,Preoptic area ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,medicine.anatomical_structure ,chemistry ,Brain lipids ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,030217 neurology & neurosurgery ,Immune-to-brain communication - Abstract
International audience; Lipids, including omega-3 polyunsaturated fatty acids (n-3-PUFAs), modulate brain-intrinsic inflammation during systemic inflammation. The vascular organ of the lamina terminalis (OVLT) is a brain structure important for immune-to-brain communication. We, therefore, aimed to profile the distribution of several lipids (e.g., phosphatidyl-choline/ethanolamine, PC/PE), including n-3-PUFA-carrying lipids (esterified in phospholipids), in the OVLT during systemic lipopolysaccharide(LPS)-induced inflammation. We injected wild type and endogenously n-3-PUFA producing fat-1 transgenic mice with LPS (i.p., 2.5 mg/kg) or PBS. Brain samples were analyzed using immunohistochemistry and high-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization orbital trapping mass spectrometry imaging (AP-SMALDI-MSI) for spatial resolution of lipids. Depending on genotype and treatment, several distinct distribution patterns were observed for lipids [e.g., lyso(L)PC (16:0)/(18:0)] proposed to be involved in inflammation. The distribution patterns ranged from being homogeneously disseminated [LPC (18:1)], absent/reduced signaling within the OVLT relative to adjacent preoptic tissue [PE (38:6)], either treatment- and genotype-dependent or independent low signal intensities [LPC (18:0)], treatment- and genotype-dependent [PC 38:6)] or independent accumulation in the OVLT [PC (38:7)], and accumulation in commissures, e.g., nerve fibers like the optic nerve [LPE (18:1)]. Overall, screening of lipid distribution patterns revealed distinct inflammation-induced changes in the OVLT, highlighting the prominent role of lipid metabolism in brain inflammation. Moreover, known and novel candidates for brain inflammation and immune-to-brain communication were detected specifically within this pivotal brain structure, a window between the periphery and the brain. The biological significance of these newly identified lipids abundant in the OVLT and the adjacent preoptic area remains to be further analyzed.
- Published
- 2019
3. Obesity Impacts Fever and Sickness Behavior During Acute Systemic Inflammation
- Author
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Lois M. Harden, Jelena Damm, Hanna Schweighöfer, Verena Peek, J. Bredehöft, and Christoph Rummel
- Subjects
0301 basic medicine ,Physiology ,Inflammation ,Disease ,Systemic inflammation ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,medicine ,Animals ,Humans ,Obesity ,Sickness behavior ,Illness Behavior ,Illness behavior ,Behavior, Animal ,business.industry ,Brain ,medicine.disease ,030104 developmental biology ,Acute Disease ,Immunology ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Obesity is reaching dramatic proportions in humans and is associated with a higher risk for cardiovascular disease, diabetes, and cognitive alterations, and a higher mortality during infection and inflammation. The focus of the present review is on the influence of obesity on the presentation of fever, sickness behavior, and inflammatory responses during acute systemic inflammation.
- Published
- 2016
4. Abstract # 3245 Modulation of the brain and peripheral response to systemic inflammation and stress by omega 3 fatty acids
- Author
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Joachim Roth, Fabian Johannes Pflieger, Christoph Rummel, Bernhard Spengler, Konstantin Mayer, Verena Peek, J. Bredehöft, Dhaka Ram Bhandari, and Sabine Schulz
- Subjects
medicine.medical_specialty ,Endocrine and Autonomic Systems ,business.industry ,Immunology ,Systemic inflammation ,Omega ,Peripheral ,Stress (mechanics) ,Behavioral Neuroscience ,Endocrinology ,Internal medicine ,Medicine ,medicine.symptom ,business - Published
- 2019
5. Abstract # 2049 Age dependent hypothalamic and pituitary responses to novel environment stress or lipopolysaccharide in rats
- Author
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Joachim Roth, S. Koenig, Christoph Rummel, F. Fuchs, J. Bredehöft, and Alexander Perniss
- Subjects
medicine.medical_specialty ,Lipopolysaccharide ,Endocrine and Autonomic Systems ,Chemistry ,medicine.medical_treatment ,Immunology ,Interleukin ,Behavioral Neuroscience ,chemistry.chemical_compound ,Cytokine ,Endocrinology ,medicine.anatomical_structure ,Anterior pituitary ,Downregulation and upregulation ,Posterior pituitary ,Internal medicine ,Median eminence ,medicine ,lipids (amino acids, peptides, and proteins) ,Hormone - Abstract
Previously, we have shown that nuclear factor interleukin (NF-IL)6 can be used as an activation marker for inflammatory lipopolysaccharide (LPS)-induced and psychological novel environment stress (NES) in the rat brain. Here, we aimed to investigate age-dependent changes of hypothalamic and pituitary responses to NES (cage switch) or LPS (100 μg/kg) in two and 24 months old rats. In the old rats, telemetric recording showed enhanced and prolonged NES-induced hyperthermia, which was accompanied by increased hypothalamic IL-6 mRNA expression and overall higher plasma corticosterone levels while corticotropin-releasing hormone mRNA-expression was only increased in young rats 90min after NES. Immunohistochemical analysis revealed a significant upregulation of NF-IL6-positive cells in the pituitary after NES or LPS-injection with higher numbers of NF-IL6 or NF-IL6-CD68-positive cells in the median eminence (LPS) or posterior pituitary (NES) of old rats compared to the young counterparts. Moreover, LPS-treatment significantly upregulated the secretion of the cytokines IL-6 and TNF α into supernatants of primary cell cultures of the anterior pituitary. Incubation with IL-6 and IL-10 antibodies prior to LPS-stimulation led to a robust decrease of IL-6- and an increase of TNF α -production by the pituitary cells in young but not in old rats. Overall, we show a prolonged hyperthermic and inflammatory response in aged animals to LPS and NES, which is linked to dysregulated pituitary cytokine interactions and modified brain cell activation (NF-IL6) in the hypothalamus-pituitary-adrenal axis.
- Published
- 2019
6. Different effects of strength and endurance exercise training on COX-2 and mPGES expression in mouse brain are independent of peripheral inflammation
- Author
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Christoph Rummel, Frank C. Mooren, J. Bredehöft, and Karsten Krüger
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Hippocampus ,Inflammation ,Running ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Endurance training ,Physiology (medical) ,Internal medicine ,Cortex (anatomy) ,Physical Conditioning, Animal ,medicine ,Animals ,RNA, Messenger ,Prostaglandin-E Synthases ,Cerebral Cortex ,biology ,business.industry ,Interleukin-6 ,Resistance training ,NF-kappa B ,Resistance Training ,030229 sport sciences ,Peripheral ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Hypothalamus ,Cyclooxygenase 2 ,biology.protein ,Physical Endurance ,Cytokines ,Cyclooxygenase ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Acute endurance exercise has been shown to modulate cyclooxygenase (COX)-2 expression, which is suggested to affect neuronal plasticity and learning. Here, we investigated the effect of regular strength and endurance training on cerebral COX-2 expression, inflammatory markers in the brain, and circulating cytokines. Male C57BL/6N mice were assigned to either a sedentary control group (CG), an endurance training group (EG; treadmill running for 30 min/day, 5 times/wk, 10 wk), or a strength training group (SG; strength training by isometric holding, same duration as EG). Four days after the last bout of exercise, blood and brain were collected and analyzed using real-time PCR, Western blot, and a multiplexed immunoassay. In EG, COX-2 mRNA expression in the cortex/hippocampus increased compared with CG. A significant increase of COX-2 protein levels was observed in both cortex/hippocampus and hypothalamus of mice from the SG. Nuclear factor (NF)κB protein levels were significantly increased in mice from both exercise groups (hypothalamus). A significant increase in the expression of microsomal prostaglandin E synthase (mPGES), an enzyme downstream of COX-2, was found in the hypothalamus of both the EG and SG. While most inflammatory factors, like IL-1α, IL-18, and IL-2, decreased after training, a positive association was found between COX-2 mRNA expression (cortex/hippocampus) and plasma IL-6 in the EG. Taken together, this study demonstrates that both endurance as well as strength training induces COX-2 expression in the cortex/hippocampus and hypothalamus of mice. A potential mediator of COX-2 expression after training might be circulating interleukin (IL)-6. However, further research is necessary to elucidate the role of inflammatory pathways on brain plasticity after training.
- Published
- 2016
7. Phospholipid species distribution patterns in the mouse vascular organ of the lamina terminalis during systemic inflammation
- Author
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Bernhard Spengler, J. Bredehöft, Christoph Rummel, Verena Peek, Joachim Roth, Dhaka Ram Bhandari, Sabine Schulz, and Konstantin Mayer
- Subjects
medicine.medical_specialty ,Pathology ,Lipopolysaccharide ,Lamina terminalis ,Fatty acid metabolism ,Endocrine and Autonomic Systems ,Immunology ,Phospholipid ,Wild type ,Lipid metabolism ,Inflammation ,Biology ,Systemic inflammation ,Behavioral Neuroscience ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Internal medicine ,medicine ,medicine.symptom - Abstract
Omega-3 fatty acids (3-FAs) modulate inflammation and brain-controlled febrile responses during inflammation. Here, we aimed to characterize the distribution and relative concentrations of several lipids (e.g. phosphatidylcholine, PC) including 3-FA-carrying lipids in a brain structure important for immune-to- brain communication, namely the vascular organ of the lamina terminalis (OVLT), during systemic lipopolysaccharide (LPS)-induced inflammation. For this purpose, wild type and fat-1 transgenic mice which produce large quantities of omega 3-FA endogenously, were stimulated with LPS (i.p., 2.5 mg/kg) or saline. Animals were sacrificed (5 h, 24 h), brains and blood samples were collected and analyzed by immunohistochemistry, high-resolution atmospheric-pressure scanning microprobe matrix assisted laser desorption/ionization ion source combined with an orbital trapping mass spectrometer and bioassays, respectively. Telemetric recordings revealed moderate hypothermia in LPS-treated fat-1 mice but fever in wildtype counterparts. Moreover, depending on genotypes and treatment, several distinct distribution patterns were observed for putative inflammation-involved phospholipids [e.g. PC(38:6), LysoPC(16:0)/(18:0), PE (P-36:4)] ranging from equal distributions, accumulation or absence within the OVLT compared to adjacent brain tissue. A localized increase of LysoPCs was indicative of enhanced LPS-induced turnover of fatty acid metabolism in the OVLT in fat-1 mice compared to wild type controls. Overall, screening of lipid distribution patterns revealed distinct inflammation-induced changes in the OVLT highlighting its prominent role for lipid metabolism and brain inflammation. New candidates for brain inflammation and immune-to-brain communication have been detected.
- Published
- 2017
8. KTQ® - ein krankenhausspezifisches Zertifizierungsverfahren
- Author
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J. Bredehöft and I. Flenker
- Subjects
Neurology (clinical) - Published
- 2001
9. Abstract # 1717 Effects of CyPPA on lipopolysaccharide-induced sickness responses, microglial activation as well as brain and systemic inflammatory mediators in mice
- Author
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Joachim Roth, S. Mazurek, Birgit Honrath, Amalia M. Dolga, Carsten Culmsee, R. Gerstberger, Christoph Rummel, and J. Bredehöft
- Subjects
medicine.medical_specialty ,Lipopolysaccharide ,Endocrine and Autonomic Systems ,Immunology ,Biology ,Systemic inflammation ,Neuroprotection ,Adenosine ,Behavioral Neuroscience ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Hypothalamus ,Internal medicine ,medicine ,biology.protein ,SOCS3 ,medicine.symptom ,Interleukin 6 ,Neuroinflammation ,medicine.drug - Abstract
N-cyclohexyl-N-[2-(3,5-dimethyl-pyrazol-1-yl)]-6-methyl-4-pyrimidinamine (CyPPA), a positive pharmacological activator of small conductance calcium-activated potassium channels, has been shown to antagonize lipopolysaccharide(LPS)-induced cytokine-expression in microglial cell cultures and, thus, has potential to treat neuroinflammation. Here, we aimed to investigate the effects of CyPPA on the brain during severe LPS-induced (2.5 mg/kg, intraperitoneal) systemic inflammation in mice. Pretreatment with CyPPA (15 mg/kg) injected 24 h prior and simultaneously with LPS-stimulation did not affect LPS-induced microglial activation, illness responses (depressed activity, anorexia and fever) and expression profiles of inflammatory mediators in the hypothalamus and in the periphery. However, CyPPA alone induced a rise in body core temperature that was accompanied by increased locomotor activity, decreased mRNA-expression of suppressor of cytokine signaling 3, increased expression of nuclear factor interleukin 6 and inhibitor of kappa B alpha in the hypothalamus while circulating cytokines were unaltered. Moreover, nuclear factor kappa B-activation was reduced in cortical neurons as revealed by western blot analyses potentially linked to some previously described neuroprotective capacities of CyPPA. Interestingly, we found reduced levels of adenosine, but a tendency of enhanced ATP and ADP in the liver of CyPPA-treated mice as measured by HPLC suggesting enhanced metabolism by CyPPA. Overall, while CyPPA might be suitable to modulate and treat some neuroinflammatory processes, the observed effects on metabolism, body core temperature and locomotor activity represent potential important side effects that should be taken into account.
- Published
- 2016
10. Zentrenbildung: was ändert sich an den Ergebnissen?
- Author
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J. Bredehöft and H. J. Bücker-Nott
- Subjects
Maternity and Midwifery ,Obstetrics and Gynecology - Published
- 2008
11. 60. Nuclear factor interleukin 6 deficient mice show alterations in the stress-axis and the serotonin metabolism
- Author
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Christoph Rummel, Denis Melo Soares, Joachim Roth, J. Bredehöft, Jelena Damm, F. Fuchs, J. Schneiders, and Rüdiger Gerstberger
- Subjects
medicine.medical_specialty ,Lipopolysaccharide ,biology ,Endocrine and Autonomic Systems ,Immunology ,Tryptophan hydroxylase ,Melatonin ,Behavioral Neuroscience ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Proopiomelanocortin ,Corticosterone ,Internal medicine ,biology.protein ,medicine ,Serotonin ,Interleukin 6 ,Serotonin transporter ,medicine.drug - Abstract
The transcription factor nuclear factor interleukin-6 (NF-IL6) has previously been proposed to be involved in stress-responses. Stress is also known to influence the serotonin system, which is important for the development of depressive disorders. Here, we aimed to further investigate the role of NF-IL6 on the stress-axis and the melatonin system using NF-IL6 deficient mice (NF-IL6KO). NF-IL6KO and wildtype mice (WT) were psychologically stressed with a novel environment followed by immunological stress (2.5 mg/kg Lipopolysaccharide, LPS) a few days later. Motor activity was measured by a telemetric system; 8 or 24 h later animals were sacrificed, brains and blood samples collected and analyzed using RT-PCR and ELISA. NF-IL6KO showed dramatically reduced activity under basal or LPS-stimulated conditions but enhanced activity in response to psychological stress compared to WT. These findings were accompanied by reduced proopiomelanocortin expression 8 h after LPS-stimulation and an abolished day-night-rhythm in corticosterone plasma levels in NF-IL6KO. In addition, NF-IL6KO showed reduced expression of the indolamine-2,3-dioxygenase 8 h after LPS-stimulation, while tryptophan hydroxylase 2 was enhanced; both known as major enzymes for serotonin metabolism. Moreover, expression of the serotonin transporter was enhanced basally and after LPS-stimulation. Overall, we strengthened the implication of NF-IL6 in stress-responses and showed, for the first time, that NF-IL6 seems to be involved in serotonin metabolism. Thus, modulation of NF-IL6-activity might have therapeutic potential for stress- or depressive disorders.
- Published
- 2014
12. Effects of Omega-3 Polyunsaturated Fatty Acids on the Formation of Adipokines, Cytokines, and Oxylipins in Retroperitoneal Adi-Pose Tissue of Mice.
- Author
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Wenderoth T, Feldotto M, Hernandez J, Schäffer J, Leisengang S, Pflieger FJ, Bredehöft J, Mayer K, Kang JX, Bier J, Grimminger F, Paßlack N, and Rummel C
- Subjects
- Animals, Mice, Male, Lipopolysaccharides, Mice, Inbred C57BL, Adipose Tissue, White metabolism, Adipose Tissue, White drug effects, Inflammation metabolism, Inflammation chemically induced, Intra-Abdominal Fat metabolism, Intra-Abdominal Fat drug effects, Oxylipins metabolism, Fatty Acids, Omega-3 metabolism, Cytokines metabolism, Adipokines metabolism
- Abstract
Oxylipins and specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated fatty acids (PUFAs) are mediators that coordinate an active process of inflammation resolution. While these mediators have potential as circulating biomarkers for several disease states with inflammatory components, the source of plasma oxylipins/SPMs remains a matter of debate but may involve white adipose tissue (WAT). Here, we aimed to investigate to what extent high or low omega (n)-3 PUFA enrichment affects the production of cytokines and adipokines (RT-PCR), as well as oxylipins/SPMs (liquid chromatography-tandem mass spectrometry) in the WAT of mice during lipopolysaccharide (LPS)-induced systemic inflammation (intraperitoneal injection, 2.5 mg/kg, 24 h). For this purpose, n-3 PUFA genetically enriched mice (FAT-1), which endogenously synthesize n-3 PUFAs, were compared to wild-type mice (WT) and combined with n-3 PUFA-sufficient or deficient diets. LPS-induced systemic inflammation resulted in the decreased expression of most adipokines and interleukin-6 in WAT, whereas the n-3-sufficient diet increased them compared to the deficient diet. The n-6 PUFA arachidonic acid was decreased in WAT of FAT-1 mice, while n-3 derived PUFAs (eicosapentaenoic acid, docosahexaenoic acid) and their metabolites (oxylipins/SPMs) were increased in WAT by genetic and nutritional n-3 enrichment. Several oxylipins/SPMs were increased by LPS treatment in WAT compared to PBS-treated controls in genetically n-3 enriched FAT-1 mice. Overall, we show that WAT may significantly contribute to circulating oxylipin production. Moreover, n-3-sufficient or n-3-deficient diets alter adipokine production. The precise interplay between cytokines, adipokines, and oxylipins remains to be further investigated.
- Published
- 2024
- Full Text
- View/download PDF
13. SK-Channel Activation Alters Peripheral Metabolic Pathways in Mice, but Not Lipopolysaccharide-Induced Fever or Inflammation.
- Author
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Bredehöft J, Dolga AM, Honrath B, Wache S, Mazurek S, Culmsee C, Schoemaker RG, Gerstberger R, Roth J, and Rummel C
- Abstract
Purpose: Previously, we have shown that CyPPA (cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine), a pharmacological small-conductance calcium-activated potassium (SK)-channel positive modulator, antagonizes lipopolysaccharide (LPS)-induced cytokine expression in microglial cells. Here, we aimed to test its therapeutic potential for brain-controlled sickness symptoms, brain inflammatory response during LPS-induced systemic inflammation, and peripheral metabolic pathways in mice., Methods: Mice were pretreated with CyPPA (15 mg/kg IP) 24 hours before and simultaneously with LPS stimulation (2.5 mg/kg IP), and the sickness response was recorded by a telemetric system for 24 hours. A second cohort of mice were euthanized 2 hours after CyPPA or solvent treatment to assess underlying CyPPA-induced mechanisms. Brain, blood, and liver samples were analyzed for inflammatory mediators or nucleotide concentrations using immunohistochemistry, real-time PCR and Western blot, or HPLC. Moreover, we investigated CyPPA-induced changes of UCP1 expression in brown adipose tissue (BAT)-explant cultures., Results: CyPPA treatment did not affect LPS-induced fever, anorexia, adipsia, or expression profiles of inflammatory mediators in the hypothalamus or plasma or microglial reactivity to LPS (CD11b staining and CD68 mRNA expression). However, CyPPA alone induced a rise in core body temperature linked to heat production via altered metabolic pathways like reduced levels of adenosine, increased protein content, and increased UCP1 expression in BAT-explant cultures, but no alteration in ATP/ADP concentrations in the liver. CyPPA treatment was accompanied by altered pathways, including NFκB signaling, in the hypothalamus and cortex, while circulating cytokines remained unaltered., Conclusion: Overall, while CyPPA has promise as a treatment strategy, in particular according to results from in vitro experiments, we did not reveal anti-inflammatory effects during severe LPS-induced systemic inflammation. Interestingly, we found that CyPPA alters metabolic pathways inducing short hyperthermia, most likely due to increased energy turnover in the liver and heat production in BAT., Competing Interests: Professor Dr Christoph Rummel reports grants from DFG FOR2107/CU 43/9-1 awarded to CC and DFG DO 1525/3-1 and personal fees from Rosalind Franklin Fellowship awarded to AMD and support by funding of the “Lung-brain axis in health and disease” initiative by the Research Campus Mid-Hessen (FCMH) awarded to CC and CR during the conduct of the study. The authors declare that they have no competing interests., (© 2022 Bredehöft et al.)
- Published
- 2022
- Full Text
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14. Replicating Roaches: A Preregistered Direct Replication of Zajonc, Heingartner, and Herman's (1969) Social-Facilitation Study.
- Author
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Halfmann E, Bredehöft J, and Häusser JA
- Subjects
- Animals, Maze Learning, Cockroaches, Social Facilitation, Task Performance and Analysis
- Abstract
Fifty years ago, Zajonc, Heingartner, and Herman (1969) conducted a famous experiment on social enhancement and inhibition of performance in cockroaches. A moderating effect of task difficulty on the effect of the presence of an audience, as revealed by impaired performance in complex tasks and enhanced performance in simple tasks, was presented as the major conclusion of this research. However, the researchers did not test this interaction statistically. We conducted a preregistered direct replication using a 2 (audience: present vs. absent) × 2 (task difficulty: runway vs. maze) between-subjects design. Results revealed main effects for task difficulty, with faster running times in the runway than the maze, and for audience, with slower running times when the audience was present than when it was absent. There was no interaction between the presence of an audience and task difficulty. Although we replicated the social-inhibition effect, there was no evidence for a social-facilitation effect.
- Published
- 2020
- Full Text
- View/download PDF
15. Visualizing and Profiling Lipids in the OVLT of Fat-1 and Wild Type Mouse Brains during LPS-Induced Systemic Inflammation Using AP-SMALDI MSI.
- Author
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Bredehöft J, Bhandari DR, Pflieger FJ, Schulz S, Kang JX, Layé S, Roth J, Gerstberger R, Mayer K, Spengler B, and Rummel C
- Subjects
- Animals, Cadherins metabolism, Inflammation chemically induced, Lipid Metabolism, Lipopolysaccharides, Male, Mice, Mice, Transgenic, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cadherins genetics, Inflammation metabolism, Lipids analysis, Organum Vasculosum metabolism
- Abstract
Lipids, including omega-3 polyunsaturated fatty acids (n-3-PUFAs), modulate brain-intrinsic inflammation during systemic inflammation. The vascular organ of the lamina terminalis (OVLT) is a brain structure important for immune-to-brain communication. We, therefore, aimed to profile the distribution of several lipids (e.g., phosphatidyl-choline/ethanolamine, PC/PE), including n-3-PUFA-carrying lipids (esterified in phospholipids), in the OVLT during systemic lipopolysaccharide(LPS)-induced inflammation. We injected wild type and endogenously n-3-PUFA producing fat-1 transgenic mice with LPS (i.p., 2.5 mg/kg) or PBS. Brain samples were analyzed using immunohistochemistry and high-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization orbital trapping mass spectrometry imaging (AP-SMALDI-MSI) for spatial resolution of lipids. Depending on genotype and treatment, several distinct distribution patterns were observed for lipids [e.g., lyso(L)PC (16:0)/(18:0)] proposed to be involved in inflammation. The distribution patterns ranged from being homogeneously disseminated [LPC (18:1)], absent/reduced signaling within the OVLT relative to adjacent preoptic tissue [PE (38:6)], either treatment- and genotype-dependent or independent low signal intensities [LPC (18:0)], treatment- and genotype-dependent [PC 38:6)] or independent accumulation in the OVLT [PC (38:7)], and accumulation in commissures, e.g., nerve fibers like the optic nerve [LPE (18:1)]. Overall, screening of lipid distribution patterns revealed distinct inflammation-induced changes in the OVLT, highlighting the prominent role of lipid metabolism in brain inflammation. Moreover, known and novel candidates for brain inflammation and immune-to-brain communication were detected specifically within this pivotal brain structure, a window between the periphery and the brain. The biological significance of these newly identified lipids abundant in the OVLT and the adjacent preoptic area remains to be further analyzed.
- Published
- 2019
- Full Text
- View/download PDF
16. Age Dependent Hypothalamic and Pituitary Responses to Novel Environment Stress or Lipopolysaccharide in Rats.
- Author
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Koenig S, Bredehöft J, Perniss A, Fuchs F, Roth J, and Rummel C
- Abstract
Previously, we have shown that the transcription factor nuclear factor interleukin (NF-IL)6 can be used as an activation marker for inflammatory lipopolysaccharide (LPS)-induced and psychological novel environment stress (NES) in the rat brain. Here, we aimed to investigate age dependent changes of hypothalamic and pituitary responses to NES (cage switch) or LPS (100 μg/kg) in 2 and 24 months old rats. Animals were sacrificed at specific time points, blood and brains withdrawn and analyzed using immunohistochemistry, RT-PCR and bioassays. In the old rats, telemetric recording revealed that NES-induced hyperthermia was enhanced and prolonged compared to the young group. Plasma IL-6 levels remained unchanged and hypothalamic IL-6 mRNA expression was increased in the old rats. Interestingly, this response was accompanied by a significant upregulation of corticotropin-releasing hormone mRNA expression only in young rats after NES and overall higher plasma corticosterone levels in all aged animals. Immunohistochemical analysis revealed a significant upregulation of NF-IL6-positive cells in the pituitary after NES or LPS-injection. In another important brain structure implicated in immune-to-brain communication, namely, in the median eminence (ME), NF-IL6-immunoreactivity was increased in aged animals, while the young group showed just minor activation after LPS-stimulation. Interestingly, we found a higher amount of NF-IL6-CD68-positive cells in the posterior pituitary of old rats compared to the young counterparts. Moreover, aging affected the regulation of cytokine interaction in the anterior pituitary lobe. LPS-treatment significantly enhanced the secretion of the cytokines IL-6 and TNFα into supernatants of primary cell cultures of the anterior pituitary. Furthermore, in the young rats, incubation with IL-6 and IL-10 antibodies before LPS-stimulation led to a robust decrease of IL-6 production and an increase of TNFα production by the pituitary cells. In the old rats, this specific cytokine interaction could not be detected. Overall, the present results revealed strong differences in the activation patterns and pathways between old and young rats after both stressors. The prolonged hyperthermic and inflammatory response seen in aged animals seems to be linked to dysregulated pituitary cytokine interactions and brain cell activation (NF-IL6) in the hypothalamus-pituitary-adrenal axis.
- Published
- 2018
- Full Text
- View/download PDF
17. Different effects of strength and endurance exercise training on COX-2 and mPGES expression in mouse brain are independent of peripheral inflammation.
- Author
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Krüger K, Bredehöft J, Mooren FC, and Rummel C
- Subjects
- Animals, Cerebral Cortex physiopathology, Cytokines metabolism, Hippocampus physiopathology, Inflammation physiopathology, Interleukin-6 metabolism, Male, Mice, Mice, Inbred C57BL, NF-kappa B metabolism, RNA, Messenger metabolism, Resistance Training methods, Running physiology, Cerebral Cortex metabolism, Cyclooxygenase 2 metabolism, Hippocampus metabolism, Inflammation metabolism, Physical Conditioning, Animal physiology, Physical Endurance physiology, Prostaglandin-E Synthases metabolism
- Abstract
Acute endurance exercise has been shown to modulate cyclooxygenase (COX)-2 expression, which is suggested to affect neuronal plasticity and learning. Here, we investigated the effect of regular strength and endurance training on cerebral COX-2 expression, inflammatory markers in the brain, and circulating cytokines. Male C57BL/6N mice were assigned to either a sedentary control group (CG), an endurance training group (EG; treadmill running for 30 min/day, 5 times/wk, 10 wk), or a strength training group (SG; strength training by isometric holding, same duration as EG). Four days after the last bout of exercise, blood and brain were collected and analyzed using real-time PCR, Western blot, and a multiplexed immunoassay. In EG, COX-2 mRNA expression in the cortex/hippocampus increased compared with CG. A significant increase of COX-2 protein levels was observed in both cortex/hippocampus and hypothalamus of mice from the SG. Nuclear factor (NF)κB protein levels were significantly increased in mice from both exercise groups (hypothalamus). A significant increase in the expression of microsomal prostaglandin E synthase (mPGES), an enzyme downstream of COX-2, was found in the hypothalamus of both the EG and SG. While most inflammatory factors, like IL-1α, IL-18, and IL-2, decreased after training, a positive association was found between COX-2 mRNA expression (cortex/hippocampus) and plasma IL-6 in the EG. Taken together, this study demonstrates that both endurance as well as strength training induces COX-2 expression in the cortex/hippocampus and hypothalamus of mice. A potential mediator of COX-2 expression after training might be circulating interleukin (IL)-6. However, further research is necessary to elucidate the role of inflammatory pathways on brain plasticity after training., (Copyright © 2016 the American Physiological Society.)
- Published
- 2016
- Full Text
- View/download PDF
18. Obesity Impacts Fever and Sickness Behavior During Acute Systemic Inflammation.
- Author
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Rummel C, Bredehöft J, Damm J, Schweighöfer H, Peek V, and Harden LM
- Subjects
- Acute Disease, Animals, Humans, Inflammation complications, Behavior, Animal physiology, Brain physiopathology, Illness Behavior physiology, Inflammation physiopathology, Obesity complications, Obesity physiopathology
- Abstract
Obesity is reaching dramatic proportions in humans and is associated with a higher risk for cardiovascular disease, diabetes, and cognitive alterations, and a higher mortality during infection and inflammation. The focus of the present review is on the influence of obesity on the presentation of fever, sickness behavior, and inflammatory responses during acute systemic inflammation., (©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.)
- Published
- 2016
- Full Text
- View/download PDF
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