Involvement of NLRP3 inflammasome in schizophrenia-like behaviour in young animals after maternal immune activation

2020 ◽  
Vol 32 (6) ◽  
pp. 321-327
Author(s):  
Letícia Ventura ◽  
Viviane Freiberger ◽  
Vinicius B. Thiesen ◽  
Paula Dias ◽  
Matheus L. Dutra ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Immune Activation ◽  
Nlrp3 Inflammasome ◽  
Biochemical Analysis ◽  
Future Studies ◽  
Maternal Immune Activation ◽  
Pyrin Domain ◽  
Behavioural Tests ◽  
The Relationship ◽  
The Brain

AbstractObjective:To evaluate the involvement of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in schizophrenia-like behaviour in young animals exposed to maternal immune activation (MIA).Methods:To this aim, on the 15th gestational day, the females received an injection of lipopolysaccharides. When the animals completed 7, 14 and 45 postnatal days, they were killed and the whole brain was dissected for biochemical analysis. Animals with 45 postnatal days were submitted to behavioural tests of locomotor activity, social interaction and stereotyped movements.Results:It was observed that the animals presented schizophrenia-like behaviour at 45 postnatal days associated with the increase of NLRP3 inflammasome expression and IL-1β levels on 7, 14 and 45 postnatal days.Conclusion:This study shows that MIA may be associated with a schizophrenia-like behaviour. This behaviour can be induced to a neuroinflammatory profile in the brain. These evidences may base future studies on the relationship between neuroinflammation and psychiatric disorders.

Maternal immune activation altered microglial immunoreactivity in the brain of postnatal day 2 rat offspring

Synapse ◽  
2018 ◽  
Vol 73 (2) ◽  
pp. e22072 ◽  
Author(s):  
Jiaxian Zhang ◽  
Yu Jing ◽  
Hu Zhang ◽  
David K. Bilkey ◽  
Ping Liu
Keyword(s):  
Immune Activation ◽  
Maternal Immune Activation ◽  
Rat Offspring ◽  
The Brain

scholarly journals HMGB1-induced NLRP3 Inflammasome Participating in Platelet Activation and Thrombocytopenia in Heatstroke

2021 ◽  
Author(s):  
Huimei Yin ◽  
Ming Wu ◽  
Yong Lu ◽  
Xinghui Wu ◽  
Baojun Yu ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Nlrp3 Inflammasome ◽  
Heat Stroke ◽  
High Mobility ◽  
Molecular Probes ◽  
Toll Like Receptor 4 ◽  
Pyrin Domain ◽  
The Relationship ◽  
Related Mortality

Abstract Background: Previous studies have suggested that NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in heat stroke (HS). As a common complication in HS, thrombocytopenia has been widely considered as a good predictor of HS-related mortality. However, little is known about the relationship between inflammasome and thrombocytopenia as well as platelet activation in HS. Methods: We established a rat HS model to investigate the roles of NLRP3 inflammasome in both platelet activation and thrombocytopenia, platelet activation was reflected with Flow cytometry while thrombocytopenia was measured by platelet count. The colocalization of NLRP3 inflammasome was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) were detected using the molecular probes. Plasma HMGB1 levels were measured by ELISA.Results: Activation of the inflammasome was detected in platelet of rats in HS. Elevated ROS activated NLRP3 inflammasome in HS group could significantly induce platelet activation and thrombocytopenia. The upregulated P-selectin (CD62P ) and decreased platelet count triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) in plasma. Moreover, inhibition of HMGB1, caspase-1, NLRP3, or ROS in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4) / advanced glycation end product (RAGE) was blocked. Conclusions: This study indicated that platelets were activated by NLRP3 inflammasome through TLR4/RAGE/HMGB1 signaling pathway. The NLRP3 inflammasome might be the potential target for HS treatment.

scholarly journals 40.3 MATERNAL IMMUNE ACTIVATION AND CHRONIC HALOPERIDOL INTERACT TO INCREASE MICROGLIAL ACTIVATION IN VIVO: DO ANTIPSYCHOTICS INFLAME THE BRAIN?

2018 ◽  
Vol 44 (suppl_1) ◽  
pp. S65-S65
Author(s):  
Marie-Caroline Cotel ◽  
Romana Polacek ◽  
Ewelina Lenartowicz ◽  
Sridhar Natesan ◽  
Jonathan Cooper ◽  
...  
Keyword(s):  
Immune Activation ◽  
Microglial Activation ◽  
Maternal Immune Activation ◽  
Chronic Haloperidol ◽  
The Brain

Maternal immune activation leads to increased nNOS immunoreactivity in the brain of postnatal day 2 rat offspring

Synapse ◽  
2017 ◽  
Vol 72 (1) ◽  
pp. e22011 ◽  
Author(s):  
Jiaxian Zhang ◽  
Yu Jing ◽  
Hu Zhang ◽  
David K. Bilkey ◽  
Ping Liu
Keyword(s):  
Immune Activation ◽  
Maternal Immune Activation ◽  
Rat Offspring ◽  
The Brain

scholarly journals Leukotriene B4 Receptors are Necessary for the Stimulation of NLRP3 Inflammasome and IL-1β Synthesis in Neutrophil-Dominant Asthmatic Airway Inflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 535
Author(s):  
Dong-Wook Kwak ◽  
Donghwan Park ◽  
Jae-Hong Kim
Keyword(s):  
Airway Inflammation ◽  
Nlrp3 Inflammasome ◽  
Leukotriene B4 ◽  
Chronic Respiratory Diseases ◽  
Asthmatic Airway ◽  
Pyrin Domain ◽  
Dust Mite ◽  
12 Lipoxygenase ◽  
The Relationship ◽  
Stimulation Of

The stimulation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and IL-1β synthesis are associated with chronic respiratory diseases such as neutrophil-dominant severe asthma. Leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophil recruitment, and its receptors BLT1 and BLT2 have been suggested to contribute to neutrophil-dominant asthmatic airway inflammation. However, the relationship between BLT1/2 and NLRP3 in neutrophil-dominant asthmatic airway inflammation has not been previously studied. In the present study, we investigated whether BLT1/2 play any roles in stimulating the NLRP3 inflammasome and IL-1βsynthesis. The blockade of BLT1 or BLT2 clearly suppressed the stimulation of the NLRP3 inflammasome and IL-1β synthesis in house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic airway inflammation. The enzymes 5-lipoxygenase and 12-lipoxygenase, which catalyze the synthesis of BLT1/2 ligands [LTB4, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), and 12-hydroxyheptadecatreinoic acid (12-HHT)], were also critically associated with the stimulation of NLRP3 and IL-1β synthesis. Together, our results suggest that the 5-/12-LOX-BLT1/2-linked cascade are necessary for the simulation of the NLRP3 inflammasome and IL-1β synthesis, thus contributing to HDM/LPS-induced neutrophil-dominant airway inflammation.

scholarly journals Interneuron Dysfunction in Syndromic Autism: Recent Advances

2015 ◽  
Vol 37 (6) ◽  
pp. 467-475 ◽  
Author(s):  
Tomoyuki Takano
Keyword(s):  
Experimental Models ◽  
Aminobutyric Acid ◽  
Inhibitory Interneurons ◽  
Gabaergic Interneurons ◽  
Inhibitory Mechanism ◽  
Future Studies ◽  
Recent Advances ◽  
Syndromic Autism ◽  
The Relationship ◽  
The Brain

Autism is an extremely heterogeneous disorder, but its frequent cooccurrence with epilepsy leads to speculation that there may be common mechanisms associated with these disorders. Inhibitory interneurons are considered to be the main cellular elements that control hyperexcitability in the brain, and interneuron dysfunction can cause pathological hyperexcitability linked to seizure susceptibility or epilepsy. This review summarizes some of the recent advances that support the relationship between interneuron dysfunction and cognitive impairment in human syndromic autism, with particular reference to the pathophysiological findings of murine experimental models of autism. Alterations in γ-aminobutyric acid (GABA)ergic circuits include a wide variety of neurobiological dysfunctions and do not simply involve the loss or gain of any given type of inhibitory mechanism. The characteristics of interneuron dysfunction in each murine model of autism differ for each syndrome, and these diversities may be due to differences in genetic backgrounds or some other currently unknown variances. Future studies should give us a greater understanding of the involvement of different classes of GABAergic interneurons and allow us to define the relationship between the precise pathophysiological mechanisms and the corresponding clinical phenotypes in autism.

scholarly journals Behavioral Alterations and Decreased Number of Parvalbumin-Positive Interneurons in Wistar Rats after Maternal Immune Activation by Lipopolysaccharide: Sex Matters

2021 ◽  
Vol 22 (6) ◽  
pp. 3274
Author(s):  
Iveta Vojtechova ◽  
Kristyna Maleninska ◽  
Viera Kutna ◽  
Ondrej Klovrza ◽  
Klara Tuckova ◽  
...  
Keyword(s):  
Immune Activation ◽  
Autism Spectrum ◽  
Startle Reaction ◽  
Adult Offspring ◽  
Behavioral Alterations ◽  
Maternal Immune Activation ◽  
Brain And Behavior ◽  
Communication Impairments ◽  
And Behavior ◽  
The Brain

Maternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery. Behavior of the offspring was examined in a comprehensive battery of tasks at postnatal days P45 and P90. Several brain parameters were analyzed at P28. The results showed that prenatal immune activation caused social and communication impairments in the adult offspring of both sexes; males were affected already in adolescence. MIA also caused prepulse inhibition deficit in females and increased the startle reaction in males. Anxiety and hypolocomotion were apparent in LPS-affected males and females. In the 28-day-old LPS offspring, we found enlargement of the brain and decreased numbers of parvalbumin-positive interneurons in the frontal cortex in both sexes. To conclude, our data indicate that sex of the offspring plays a crucial role in the development of the MIA-induced behavioral alterations, whereas changes in the brain apparent in young animals are sex-independent.

Grenzenlose Verantwortung

2010 ◽  
Vol 2010 (1) ◽  
pp. 5-22
Author(s):  
Ralf Becker
Keyword(s):  
Personal Freedom ◽  
The Relationship ◽  
The Brain

The article examines the relationship between freedom, guilt and responsibility in Dostojewski’s and Sartre’s works. Both attribute a great measure of personal freedom to man. Therefore, they do not tolerate excuses. Whoever is free, carries responsibility and gets caught up in guilt. Dostojewski’s focus is mainly on guilt, Sartre’s is on responsibility. They share the conviction that we can delegate responsibility for our actions or our way of living neither to a whole, of which we are a part, like society (the ,milieu'), nor to a part, for which we are the whole, like the ,brain' or the ,genes'. In that sense, Dostojewski’s and Sartre’s attempts at an ethic of responsibility also offer convincing arguments against determinism.

EXPERIMENTAL ASSESSMENT OF THE NANOPARTICLES TOXICITY OF NICKEL OXIDE IN TWO SIZES IN THE SUBCHRONIC EXPERIMENT

2018 ◽  
pp. 30-35
Author(s):  
M.P. Sutunkova ◽  
B.A. Katsnelson ◽  
L.I. Privalova ◽  
S.N. Solovjeva ◽  
V.B. Gurvich ◽  
...  
Keyword(s):  
Nickel Oxide ◽  
Nervous Activity ◽  
Equal Mass ◽  
The Body ◽  
Subchronic Toxicity ◽  
Physiological Mechanisms ◽  
Nickel Oxide Nanoparticles ◽  
The Relationship ◽  
The Brain ◽  
Nanoparticles Toxicity

We conducted a comparative assessment of the nickel oxide nanoparticles toxicity (NiO) of two sizes (11 and 25 nm) according to a number of indicators of the body state after repeated intraperitoneal injections of these particles suspensions. At equal mass doses, NiO nanoparticles have been found to cause various manifestations of systemic subchronic toxicity with a particularly pronounced effect on liver, kidney function, the body’s antioxidant system, lipid metabolism, white and red blood, redox metabolism, spleen damage, and some disorders of nervous activity allegedly related to the possibility of nickel penetration into the brain from the blood. The relationship between the diameter and toxicity of particles is ambiguous, which may be due to differences in toxicokinetics, which is controlled by both physiological mechanisms and direct penetration of nanoparticles through biological barriers and, finally, unequal solubility.

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