Following diagnosis but before treatment, up to 30% of breast cancer patients report behavioral side effects (e.g., anxiety, depression, memory impairment). Our rodent mammary tumor model ...recapitulates aspects of these behavioral sequelae, as well as elevated circulating and brain inflammatory mediators. Neuroinflammation is a proposed mechanism underlying the etiology of mood disorders and cognitive deficits, and therefore may be contributing to tumor‐associated behavioral side effects. The cellular mechanisms by which tumor‐induced neuroinflammation occurs remain unknown, making targeted treatment approaches inaccessible. Here, we tested the hypotheses that microglia are the primary cells driving tumor‐induced neuroinflammation and behavioral side effects. Young adult female BALB/c mice were induced with a 67NR mammary tumor; tumor‐free controls underwent a sham surgery. Mammary tumors increased IBA1+ and GFAP+ staining in the amygdala and hippocampus relative to tumor‐free controls. However, tumors did not alter gene expression of Percoll‐enriched microglia isolated from the whole brain. While cognitive, social, and anhedonia‐like behaviors were not altered in tumor‐bearing mice, tumors increased central tendency in the open‐field test; microglia depletion did not reverse this effect. Brain region RT‐qPCR data indicated that microglia depletion attenuated tumor‐induced elevations of neuroinflammatory gene expression in a region‐ and mediator‐specific manner. These results indicate a causal role of microglia in tumor‐induced neuroinflammation. This research advances our understanding of the cellular mechanisms underlying tumor‐induced neuroinflammation in order to understand how brain responses (e.g., behavior) may be altered with subsequent cancer‐related immune challenges.
An orthotopic, non‐metastatic mammary tumor increased IBA1+ percent area staining in the hippocampus and amygdala, and increased gene expression of neuroinflammatory mediators in the amygdala. However, a mammary tumor did not alter gene expression of Percoll‐enriched microglia isolated from the whole brain; region‐specific isolation is warranted. Microglia depletion via PLX5622 attenuated tumor‐induced increases of neuroinflammatory gene expression in the amygdala. Altogether, the data indicate that microglia contribute to mammary tumor‐induced neuroinflammation in a female mouse model.
Introduction
Depression is the most common comorbidity of migraine. The brain of migraineurs with depression shows differences compared to migraine only or depression only patients. The comorbidity ...may affect specific regions such as the periaqueductal gray matter (PAG) which is important in negative emotion regulation and pain modulatory system.
Objectives
We hypothesized that the alterations in PAG functional connectivity (FC) may play a role in migraineurs vulnerability for depression.
Methods
A resting-state fMRI was conducted with 34 episodic migraine without aura patients and 41 control subjects. All participants were medication free and they did not have any psychiatric or chronic disorders. Depressive symptoms were measured with Zung Self-Rating Depression Scale. To investigate the relationship between depressive symptoms and PAG functional connectivity, Zung scores were used as covariates in each groups’ PAG-FC analysis using the Statistical Parametric Mapping (SPM12) toolbox in MATLAB environment.
Results
There were no significant difference between migraine and control group in Zung scores (p=0.394). Negative correlation was found between Zung scores and PAG-FC with thalamus, fusiform gyrus, middle occipital gyrus and calcarine (p
FWE
<0.05) in migraine group. However, there was no significant correlation between Zung scores and PAG-FC in healthy control group.
Conclusions
Our results suggest that PAG-FC with emotion and pain processing areas is affected by depressive symptoms in migraine patients, but not in healthy controls. Migraine patients without comorbid depression might have vulnerable neuronal pathways for depressive symptoms. A follow-up of these patients could be interesting to determine whether these connectivity alterations predict the possible comorbid depression.
Disclosure
Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002, KTIA_13_NAPA-II/14, KTIA_NAP_13-1-2013- 0001, KTIA_NAP_13-2- 2015-0001); 2020-4.1.1.-TKP2020; ERA PerMed (2019-2.1.7-ERA-NET-2020-00005); ÚNKP-21-4-I-SE-15 (DB).
It is poorly understood how solid peripheral tumors affect brain neuroimmune responses despite the various brain-mediated side effects and higher rates of infection reported in cancer patients. We ...hypothesized that chronic low-grade peripheral tumor-induced inflammation conditions microglia to drive suppression of neuroinflammatory responses to a subsequent peripheral immune challenge. Here, Balb/c murine mammary tumors attenuated the microglial inflammatory gene expression responses to lipopolysaccharide (LPS) and live Escherichia coli (E. coli) challenges and the fatigue response to an E. coli infection. In contrast, the inflammatory gene expression in response to LPS or a toll-like receptor 2 agonist of Percoll-enriched primary microglia cultures was comparable between tumor-bearing and -free mice, as were the neuroinflammatory and sickness behavioral responses to an intracerebroventricular interleukin (IL)-1β injection. These data led to the hypothesis that Balb/c mammary tumors blunt the neuroinflammatory responses to an immune challenge via a mechanism involving tumor suppression of the peripheral humoral response. Balb/c mammary tumors modestly attenuated select circulating cytokine responses to LPS and E. coli challenges. Further, a second mammary tumor/mouse strain model (E0771 tumors in C57Bl/6 mice) displayed mildly elevated inflammatory responses to an immune challenge. Taken together, these data indicate that tumor-induced suppression of neuroinflammation and sickness behaviors may be driven by a blunted microglial phenotype, partly because of an attenuated peripheral signal to the brain, which may contribute to infection responses and behavioral side effects reported in cancer patients. Finally, these neuroimmune effects likely vary based on tumor type and/or host immune phenotype.
The Beam Conditions Monitor (BCM) 1,5 of the ATLAS experiment protects the Inner Detector silicon trackers from high radiation doses caused by LHC beam incidents. It uses 161×1cm2500μm thick ...polycrystalline chemical vapor deposition (pCVD) diamond sensors arranged in 8 positions around the interaction point. Time difference measurements with 2.56GHz sampling are performed to distinguish between collision and background. In case of excessive beam background due to beam incidents, the BCM can trigger a beam abort. A FPGA based readout system performs the online data analysis and interfaces the results to ATLAS and the beam abort system. The diamond sensors, the detector modules and their readout system are described. Results of the operation with the first LHC beams are reported. Results of commissioning and timing measurements with cosmic muons in preparation for first LHC collisions are summarized.
Diamond pixel modules and the ATLAS beam conditions monitor Dobos, D.; Pernegger, Heinz
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2011, Letnik:
628, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Chemical vapor deposition diamonds are considered among possible sensor materials for the next pixel upgrade in ATLAS. Full size diamond pixel modules have been constructed to the specification of ...the ATLAS Pixel Detector using poly-crystalline CVD diamond sensors to develop the production techniques required for industrial production. Those modules were tested in the lab and testbeam. Additionally we will present results of diamond pixel modules using single-crystal diamonds and results of proton irradiations up to 1.8 ×10
16
protons/cm
2. The ATLAS Beam Conditions Monitors (BCM) main purpose is to protect the experiments silicon tracker from beam incidents. In total 16
1
×
1
cm
2
500
μ
m
thick diamond pCVD sensors are used in eight positions around the LHC interaction point. They perform time difference measurements with sub nanosecond resolution to distinguish between particles from a collision and spray particles from a beam incident; an abundance of the latter can lead the BCM to provoke an abort of LHC beam. The BCM diamond detector modules, their readout system and the algorithms used to detect beam incidents are described. Results of the BCM operation with circulating LHC beams and its commissioning with first LHC collisions are reported.
To analyse the dynamics of macronutrients in breast milk in Slovakian women and compare the dynamics between mothers of hospitalized newborns and donors of human breast milk relative to the ...gestational age of their babies.
Human milk samples were collected from 101 breastfeeding women and analysed once or repeatedly from September 2017 to August 2018. Group A consisted of 79 mothers of newborns hospitalized at the Neonatal Department of Intensive Medicine (NDIM) of whom 69 were mothers of premature newborns (subgroup A1) and 10 were mothers of term babies (subgroup A2). Group B consisted of 22 breast milk donors registered at the Human Milk Bank at National Institute of Children's Diseases (NICHD). Of these, 4 were mothers of premature newborns (subgroup B1) and 18 were mothers of term newborns (subgroup B2). From subgroup A1, we chose two mothers, one with a hypotrophic newborn and another with a eutrophic newborn. The results were obtained by using the MIRIS breast‑milk analyzer.
The overall dynamics of macronutrients correspond with other studies, however, we demonstrated that the level of macronutrients in individual cases were different.
The determination of macronutrients in human milk is essential in neonatal care. It provides information about the nutritional value of breast milk and helps to optimise nutrition according to the individual needs of newborns (Fig. 10, Ref. 16).
Diamond pixel modules Asner, D.; Barbero, M.; Bellini, V. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2011, Letnik:
636, Številka:
1
Journal Article
Recenzirano
With the commissioning of the LHC in 2010 and upgrades expected in 2015, ATLAS and CMS are planning to upgrade their innermost tracking layers with radiation hard technologies. Chemical Vapor ...Deposition diamond has been used extensively in beam conditions monitors as the innermost detectors in the highest radiation areas of BaBar, Belle, CDF and all LHC experiments. This material is now being considered as a sensor material for use very close to the interaction region where the most extreme radiation conditions exist. Recently the RD42 collaboration constructed, irradiated and tested polycrystalline and single-crystal chemical vapor deposition diamond sensors to the highest fluences expected at the super-LHC. We present beam test results of chemical vapor deposition diamond up to fluences of 1.8×10
16
protons/cm
2 illustrating that both polycrystalline and single-crystal chemical vapor deposition diamonds follow a single damage curve. We also present beam test results of irradiated complete diamond pixel modules.
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