scholarly journals Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma

2022 ◽  
Vol 23 (2) ◽  
pp. 655
Author(s):  
Tin-Tin Win-Shwe ◽  
Rie Yanagisawa ◽  
Thet-Thet Lwin ◽  
Fumitaka Kawakami ◽  
Eiko Koike ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Object Recognition ◽  
Mast Cells ◽  
Flame Retardant ◽  
Dietary Exposure ◽  
Blue Staining ◽  
Oxidative Stress Marker ◽  
Heme Oxygenase 1 ◽  
Allergic Asthmatic ◽  
The Brain

Tris (2-butoxyethyl) phosphate (TBEP) is an organophosphate flame retardant and used as a plasticizer in various household products such as plastics, floor polish, varnish, textiles, furniture, and electronic equipment. However, little is known about the effects of TBEP on the brain and behavior. We aimed to examine the effects of dietary exposure of TBEP on memory functions, their-related genes, and inflammatory molecular markers in the brain of allergic asthmatic mouse models. C3H/HeJSlc male mice were given diet containing TBEP (0.02 (TBEP-L), 0.2 (TBEP-M), or 2 (TBEP-H) μg/kg/day) and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. A novel object recognition test was conducted in each mouse at 11 weeks old. The hippocampi were collected to detect neurological, glia, and immunological molecular markers using the real-time RT-PCR method and immunohistochemical analyses. Mast cells and microglia were examined by toluidine blue staining and ionized calcium-binding adapter molecule (Iba)-1 immunoreactivity, respectively. Impaired discrimination ability was observed in TBEP-H-exposed mice with or without allergen. The mRNA expression levels of N-methyl-D aspartate receptor subunits Nr1 and Nr2b, inflammatory molecular markers tumor necrosis factor-α oxidative stress marker heme oxygenase 1, microglia marker Iba1, and astrocyte marker glial fibrillary acidic protein were significantly increased in TBEP-H-exposed mice with or without allergen. Microglia and mast cells activation were remarkable in TBEP-H-exposed allergic asthmatic mice. Our results indicate that chronic exposure to TBEP with or without allergen impaired object recognition ability accompanied with alteration of molecular expression of neuronal and glial markers and inflammatory markers in the hippocampus of mice. Neuron-glia-mast cells interaction may play a role in TBEP-induced neurobehavioral toxicity.

scholarly journals Protective Effects of Taurine Chloramine on Experimentally Induced Colitis: NFκB, STAT3, and Nrf2 as Potential Targets

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 479
Author(s):  
Seong Hoon Kim ◽  
Hye-Won Yum ◽  
Seung Hyeon Kim ◽  
Wonki Kim ◽  
Su-Jung Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Parent Compound ◽  
Oxidative Stress Marker ◽  
Heme Oxygenase 1 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Protective Effects ◽  
Taurine Chloramine ◽  
Proinflammatory Mediators ◽  
Experimentally Induced

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3.

scholarly journals Brain mast cells link the immune system to anxiety-like behavior

2008 ◽  
Vol 105 (46) ◽  
pp. 18053-18057 ◽  
Author(s):  
Katherine M. Nautiyal ◽  
Ana C. Ribeiro ◽  
Donald W. Pfaff ◽  
Rae Silver
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Neural Systems ◽  
Loss Of Function ◽  
Littermate Control ◽  
Cytokines And Chemokines ◽  
Function Models ◽  
The Brain

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

scholarly journals UV-induced neuronal degeneration in the rat cerebral cortex

2021 ◽  
Author(s):  
Mariko Nakata ◽  
Masayuki Shimoda ◽  
Shinya Yamamoto
Keyword(s):  
Uv Irradiation ◽  
Neuronal Degeneration ◽  
Uv Light ◽  
Brain Lesion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Focal Brain Injury ◽  
The Brain ◽  
And Oxidative Stress

Abstract Irradiation with ultraviolet (UV) light on the cortical surface can induce a focal brain lesion (UV lesion) in rodents. In the present study, we investigated the process of establishing a UV lesion. Rats underwent UV irradiation (365 nm wavelength, 2.0 mWh) over the dura, and time-dependent changes in the cortical tissue were analyzed histologically. We found that the majority of neurons in the lesion started to degenerate within 24 hours and the rest disappeared within 5 days after irradiation. UV-induced neuronal degeneration progressed in a layer-dependent manner. Moreover, UV-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity and heme oxygenase-1 (HO-1) immunoreactivity were also detected. These findings suggest that UV irradiation in the brain can induce gradual neural degeneration and oxidative stress. Importantly, UV vulnerability may vary among cortical layers. UV-induced cell death may be due to apoptosis; however, there remains a possibility that UV-irradiated cells were degenerated via processes other than apoptosis. The UV lesion technique will not only assist in investigating brain function at a targeted site but may also serve as a pathophysiological model of focal brain injury and/or neurodegenerative disorders.

scholarly journals Aicardi-Goutières syndrome-associated mutation at ADAR1 gene locus activates innate immune response in mouse brain

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xinfeng Guo ◽  
Clayton A. Wiley ◽  
Richard A. Steinman ◽  
Yi Sheng ◽  
Beihong Ji ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Rna Editing ◽  
Mouse Brain ◽  
Mutant Mouse ◽  
Cell Types ◽  
Mutant Mice ◽  
Blue Staining ◽  
Sequencing Analysis ◽  
Elevated Type ◽  
The Brain

Abstract Background Aicardi-Goutières syndrome (AGS) is a severe infant or juvenile-onset autoimmune disease characterized by inflammatory encephalopathy with an elevated type 1 interferon-stimulated gene (ISG) expression signature in the brain. Mutations in seven different protein-coding genes, all linked to DNA/RNA metabolism or sensing, have been identified in AGS patients, but none of them has been demonstrated to activate the IFN pathway in the brain of an animal. The molecular mechanism of inflammatory encephalopathy in AGS has not been well defined. Adenosine Deaminase Acting on RNA 1 (ADAR1) is one of the AGS-associated genes. It carries out A-to-I RNA editing that converts adenosine to inosine at double-stranded RNA regions. Whether an AGS-associated mutation in ADAR1 activates the IFN pathway and causes autoimmune pathogenesis in the brain is yet to be determined. Methods Mutations in the ADAR1 gene found in AGS patients were introduced into the mouse genome via CRISPR/Cas9 technology. Molecular activities of the specific p.K999N mutation were investigated by measuring the RNA editing levels in brain mRNA substrates of ADAR1 through RNA sequencing analysis. IFN pathway activation in the brain was assessed by measuring ISG expression at the mRNA and protein level through real-time RT-PCR and Luminex assays, respectively. The locations in the brain and neural cell types that express ISGs were determined by RNA in situ hybridization (ISH). Potential AGS-related brain morphologic changes were assessed with immunohistological analysis. Von Kossa and Luxol Fast Blue staining was performed on brain tissue to assess calcification and myelin, respectively. Results Mice bearing the ADAR1 p.K999N were viable though smaller than wild type sibs. RNA sequencing analysis of neuron-specific RNA substrates revealed altered RNA editing activities of the mutant ADAR1 protein. Mutant mice exhibited dramatically elevated levels of multiple ISGs within the brain. RNA ISH of brain sections showed selective activation of ISG expression in neurons and microglia in a patchy pattern. ISG-15 mRNA was upregulated in ADAR1 mutant brain neurons whereas CXCL10 mRNA was elevated in adjacent astroglia. No calcification or gliosis was detected in the mutant brain. Conclusions We demonstrated that an AGS-associated mutation in ADAR1, specifically the p.K999N mutation, activates the IFN pathway in the mouse brain. The ADAR1 p.K999N mutant mouse replicates aspects of the brain interferonopathy of AGS. Neurons and microglia express different ISGs. Basal ganglia calcification and leukodystrophy seen in AGS patients were not observed in K999N mutant mice, indicating that development of the full clinical phenotype may need an additional stimulus besides AGS mutations. This mutant mouse presents a robust tool for the investigation of AGS and neuroinflammatory diseases including the modeling of potential “second hits” that enable severe phenotypes of clinically variable diseases.

The lysosomal protease cathepsin D is efficiently sorted to and secreted from regulated secretory compartments in the rat basophilic/mast cell line RBL

2000 ◽  
Vol 113 (18) ◽  
pp. 3289-3298 ◽  
Author(s):  
A. Dragonetti ◽  
M. Baldassarre ◽  
R. Castino ◽  
M. Demoz ◽  
A. Luini ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Line ◽  
Cathepsin D ◽  
Secretory Granules ◽  
Bioactive Molecules ◽  
Blue Staining ◽  
Lysosomal Protease ◽  
Mannose 6 Phosphate ◽  
Mast Cell Line

Basophils and mast cells contain a peculiar class of inflammatory granules that discharge their content upon antigen-mediated crosslinking of IgE-membrane receptors. The pathways for granule biogenesis and exocytosis in these cells are still largely obscure. In this study we employed the rat basophilic leukemia (RBL)/mast cell line to verify the hypothesis that inflammatory granules share common bioactive molecules and functional properties with lysosomes. We demonstrate that inflammatory granules, as identified by the monoclonal 5G10 antibody (which recognises an integral membrane protein) or by Toluidine Blue staining, have an intralumenal acidic pH, possess lysosomal enzymes and are accessible by fluid-phase and membrane endocytosis markers. In addition, we studied the targeting, subcellular localisation and regulated secretion of the lysosomal aspartic protease cathepsin D (CD) as affected by IgE receptor stimulation in order to obtain information on the pathways for granule biogenesis and exocytosis. Stimulation with DNP-BSA of specific IgE-primed RBL cells led to a prompt release of processed forms of CD, along with other mature lysosomal hydrolases. This release could be prevented by addition of EGTA, indicating that it was dependent on extracellular calcium influx. Antigen stimulation also induced exocytosis of immature CD forms accumulated by ammonium chloride, suggesting the existence of an intermediate station in the pathway for granule biogenesis still sensitive to regulated exocytosis. The targeting of molecules to secretory granules may occur via either a mannose-6-phosphate-dependent or mannose-6-phosphate-independent pathway. We conclude that endosomes and lysosomes in basophils/mast cells can act as regulated secretory granules or actually identify with them.

Abstract TP102: Modulation of Neuroinflammation by Haptoglobin Reduces Oxidative Stress and Improves ICH Outcomes

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jenna Leclerc ◽  
Alex Dang ◽  
Juan Santiago-Moreno ◽  
Sylvain Dore
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Functional Outcomes ◽  
Ferric Iron ◽  
Heme Oxygenase 1 ◽  
High Morbidity ◽  
Blood Components ◽  
Autologous Whole Blood ◽  
The Brain ◽  
Histological Staining

Intracerebral hemorrhage (ICH) is a stroke subtype associated with high morbidity and mortality. With breakdown of the blood-brain barrier and entry of toxic blood components and metabolites within the brain, a highly oxidative environment ensues and leads to a toxic neuroinflammatory cascade. A major cause of the debilitation following brain hemorrhage is due to the direct toxicity of blood components, notably hemoglobin (Hb), the most upstream precipitating factor in the cascade. The acute phase plasma protein haptoglobin (Hp) binds Hb and inhibits its cytotoxic, pro-oxidative, and pro-inflammatory properties. In this study, we investigated whether the local and specific overexpression of Hp would aid in the safe detoxification and clearance of free Hb, thereby protecting the neuropil from Hb-mediated oxidative stress and improving ICH outcomes. Hp was overexpressed locally within the brain using uniquely designed adeno-associated viral vectors and ICH was induced using the intrastriatal autologous whole blood injection model. Functional outcomes were assessed by a 24-point neurological deficit score. At 72h post-hemorrhage, mice were sacrificed and brains collected for histological staining. Hp-overexpressing mice demonstrated smaller lesion volumes (p<0.05) with less blood accumulation (p<0.05) and improve neurologic status after ICH (p<0.05) when compared to an identically treated control group (n=11-13/group). Histological staining for Iba-1, GFAP, heme oxygenase-1, 4-hydroxynonenal, ferric iron, and myeloperoxidase was performed and revealed: 1) significantly less heme oxygenase-1 expression and lipid peroxidation, 2) a trend towards reduced peripheral neutrophil infiltration, 3) significantly increased cortical microgliosis and cortical and striatal astrogliosis, and 4) no changes in ferric iron content or striatal microgliosis. In conclusion, Hp overexpression in the brain reduces ICH-induced brain injury and improves functional outcomes. Locally modulating brain Hp levels could represent an important clinically relevant strategy for the treatment of ICH.

scholarly journals A New Paradigm for Training Hyperactive Dopamine Transporter Knockout Rats: Influence of Novel Stimuli on Object Recognition

2021 ◽  
Vol 15 ◽  
Author(s):  
Natalia P. Kurzina ◽  
Anna B. Volnova ◽  
Irina Y. Aristova ◽  
Raul R. Gainetdinov
Keyword(s):  
Object Recognition ◽  
Dopamine Transporter ◽  
Cognitive Task ◽  
Recognition Task ◽  
Long Term Memory ◽  
New Paradigm ◽  
Dopaminergic Transmission ◽  
Novel Objects ◽  
High Level ◽  
The Brain

Attention deficit hyperactivity disorder (ADHD) is believed to be connected with a high level of hyperactivity caused by alterations of the control of dopaminergic transmission in the brain. The strain of hyperdopaminergic dopamine transporter knockout (DAT-KO) rats represents an optimal model for investigating ADHD-related pathological mechanisms. The goal of this work was to study the influence of the overactivated dopamine system in the brain on a motor cognitive task fulfillment. The DAT-KO rats were trained to learn an object recognition task and store it in long-term memory. We found that DAT-KO rats can learn to move an object and retrieve food from the rewarded familiar objects and not to move the non-rewarded novel objects. However, we observed that the time of task performance and the distances traveled were significantly increased in DAT-KO rats in comparison with wild-type controls. Both groups of rats explored the novel objects longer than the familiar cubes. However, unlike controls, DAT-KO rats explored novel objects significantly longer and with fewer errors, since they preferred not to move the non-rewarded novel objects. After a 3 months’ interval that followed the training period, they were able to retain the learned skills in memory and to efficiently retrieve them. The data obtained indicate that DAT-KO rats have a deficiency in learning the cognitive task, but their hyperactivity does not prevent the ability to learn a non-spatial cognitive task under the presentation of novel stimuli. The longer exploration of novel objects during training may ensure persistent learning of the task paradigm. These findings may serve as a base for developing new ADHD learning paradigms.

scholarly journals Human brain harbors single nucleotide somatic variations in functionally relevant genes possibly mediated by oxidative stress

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2520 ◽  
Author(s):  
Anchal Sharma ◽  
Asgar Hussain Ansari ◽  
Renu Kumari ◽  
Rajesh Pandey ◽  
Rakhshinda Rehman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Corpus Callosum ◽  
Human Brain ◽  
Frontal Cortex ◽  
Oxidative Stress Marker ◽  
Somatic Variation ◽  
Single Nucleotide ◽  
Normal Human Brain ◽  
Normal Human ◽  
The Brain

Somatic variation in DNA can cause cells to deviate from the preordained genomic path in both disease and healthy conditions. Here, using exome sequencing of paired tissue samples, we show that the normal human brain harbors somatic single base variations measuring up to 0.48% of the total variations. Interestingly, about 64% of these somatic variations in the brain are expected to lead to non-synonymous changes, and as much as 87% of these represent G:C>T:A transversion events. Further, the transversion events in the brain were mostly found in the frontal cortex, whereas the corpus callosum from the same individuals harbors the reference genotype. We found a significantly higher amount of 8-OHdG (oxidative stress marker) in the frontal cortex compared to the corpus callosum of the same subjects (p<0.01), correlating with the higher G:C>T:A transversions in the cortex. We found significant enrichment for axon guidance and related pathways for genes harbouring somatic variations. This could represent either a directed selection of genetic variations in these pathways or increased susceptibility of some loci towards oxidative stress. This study highlights that oxidative stress possibly influence single nucleotide somatic variations in normal human brain.

scholarly journals Analysis of the presence and location of mast cells in periapical cysts and periapical granulomas

2016 ◽  
Vol 64 (4) ◽  
pp. 376-381 ◽  
Author(s):  
Emerson Filipe de Carvalho NOGUEIRA ◽  
Elder Gyress Feitosa FARIAS ◽  
Luciano Barreto SILVA ◽  
Alexandrino Pereira dos SANTOS NETO ◽  
Emanuel Sávio de Souza ANDRADE ◽  
...  
Keyword(s):  
Mast Cells ◽  
Granulation Tissue ◽  
Blue Staining ◽  
Double Blind Study ◽  
Double Blind ◽  
Cross Sectional ◽  
Periapical Granuloma ◽  
Staining Methods ◽  
Periapical Cyst ◽  
Quantitative Descriptive

ABSTRACT Objective: The aim of the present study was to locate mast cells in chronic periapical lesions (granulomas and cysts) by using histochemical techniques and toluidine blue staining. Methods: A quantitative, descriptive, cross-sectional and retrospective research was performed. The sample was obtained from histopathological reports in the archives of the laboratory of surgical pathology of the University of Pernambuco between November 2014 and May 2015. Results: Sixteen cases of granuloma and 21 cases of periapical cysts were selected. The stained slides were analyzed by two examiners at different times, in a double-blind study. Mast cells were found in 13 (61.9%) of the periapical cyst cases, located in the capsule of the lesion. In the periapical granuloma cases, mast cells were found in eight cases (50%), located in the granulation tissue. Conclusion: Mast cells were detected in both cysts and periapical granuloma, located in the capsule and granulation tissue, respectively. Mast cells were more prevalent in periapical cysts than in periapical granuloma.

Sign in / Sign up

Export Citation Format

Share Document