Chronic acrylamide exposure induced glia cell activation, NLRP3 infl-ammasome upregulation and cognitive impairment

2020 ◽  
Vol 393 ◽  
pp. 114949 ◽  
Author(s):  
Ying Liu ◽  
Xing Zhang ◽  
Dandan Yan ◽  
Yiqi Wang ◽  
Na Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cell Activation ◽  
Glia Cell

scholarly journals Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish

10.3791/56249 ◽  
2017 ◽  
Author(s):  
Federica M. Conedera ◽  
Petra Arendt ◽  
Carolyn Trepp ◽  
Markus Tschopp ◽  
Volker Enzmann
Keyword(s):  
Retinal Degeneration ◽  
Cell Activation ◽  
Glia Cell

scholarly journals INT-777 Improves Cognitive Impairment after Sepsis by Attenuating Neuroinflammation Through the TGR5/cAMP/PKA/CREB Signaling Axis in Rats

2020 ◽  
Author(s):  
Peng Jin ◽  
Shuixiang Deng ◽  
Mi Tian ◽  
Pengju Wei ◽  
Yao Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Survival Rate ◽  
Cell Activation ◽  
Cecal Ligation ◽  
Clinical Score ◽  
Inflammatory Factors ◽  
Experimental Sepsis ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Sepsis Survivors

Abstract Background: Sepsis survivors are left with significant cognitive and behavioral impairments after discharge, but research on the relevant mechanisms and interventions remains lacking. TGR5 plays a neuroprotective role in many neurologic disease models through different mechanisms. To date, no studies have assessed the effects of TGR5 on neuroinflammation or cognitive or behavioral changes in sepsis models.Methods: A total of 267 eight-week-old male Sprague-Dawley rats were used in this study. Sepsis was induced by cecal ligation and puncture (CLP). All animals received volume resuscitation. The rats were given TGR5 CRISPR oligonucleotide intracerebroventricularly 48 hours before CLP surgery. INT-777 was administered intranasally 1 hour after CLP, and the cAMP inhibitor SQ22536 was administered intracerebroventricularly 1 hour after CLP. Survival rate, bodyweight change, clinical score, neurobehavioral tests, western blot, and immunofluorescence staining were performed. The cognitive function of rats was measured by Morris water maze during 15-20 days after CLP.Results: The expression of TGR5 in the rat hippocampus was upregulated and peaked at 3 days after CLP. The survival rate of rats after CLP was less than 50%, and the growth rate in terms of weight was significantly decreased, while these changes were not improved by INT-777 treatment. However, INT-777 treatment reduced the clinical scores of rats at 24 hours after CLP. On day 15 and later, the surviving mice completed a series of behavioral tests. CLP rats showed spatial and memory deficits and anxiety-like behaviors, and INT-777 treatment significantly improved these effects. Mechanistically, immunofluorescence analysis showed that INT-777 treatment reduced the number of microglia in the hippocampus, neutrophil infiltration and the expression of inflammatory factors after CLP in rats. Moreover, INT-777 treatment significantly increased the expression of TGR5, cAMP, p-PKA, and p-CREB and downregulated the expression of IL-1β, IL-6 and TNF-α. CRISPR-mediated TGR5 knockdown and SQ22536 treatment abolished the neuroprotective effects of TGR5 activation after CLP.Conclusion: This study demonstrates that INT-777 treatment reduced neuroinflammation and microglial cell activation, and then improved cognitive impairment in the experimental sepsis rats. TGR5 has translational potential as a therapeutic target to improve neurological outcomes in sepsis survivors.

scholarly journals Qiang Xin 1 Formula Suppresses Excessive Pro-inflammatory Cytokine Responses and Microglia Activation to Prevent Cognitive Impairment and Emotional Dysfunctions in Experimental Sepsis

2019 ◽  
Author(s):  
Xuerui Wang ◽  
Xiaolong Xu ◽  
Yuhong Guo ◽  
Po Huang ◽  
Yanxiang Ha ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Signaling Pathway ◽  
Microglial Activation ◽  
Inflammatory Cytokine ◽  
Cell Activation ◽  
Cytokine Production ◽  
Behavioral Changes ◽  
Microglia Cell ◽  
Emotional Dysfunction

Abstract Background: Sepsis commonly leads to acute and long-term cognitive and affective impairments which are associated with increased mortality in patients. Neuroinflammation characterized by excessive cytokine release and immune cell activation underlies the behavioral changes associated with sepsis. We previously reported that the administration of a traditional Chinese herbal Qiang Xin 1 (QX1) formula improves survival in septic mice. This study was performed to better understand the effects and the mechanisms of QX1 formula treatment on behavioral changes in septic model. Methods: A preclinical septic model was induced by cecal ligation and puncture in mice. QX1 formula was orally administrated daily. Behavior test including Morris water maze, novel object recognition testing, elevated plus maze and open field testing was performed. Elisa, immunofluorescence, microarray analysis, and Real-time PCR were analyzed. Results: QX1 formula administration significantly improved survival, alleviated overall cognitive impairment and emotional dysfunction in septic mice. QX1 formula administration dramatically inhibited short and long-term excessive pro-inflammatory cytokine production both peripherally and centrally, and was accompanied by diminished microglial activation in septic mice. Biological processes including synaptic transmission, microglia cell activation, cytokine production, microglia cell polarization, as well as inflammatory responses related to signaling pathways including the MAPK signaling pathway and the NF-κB signaling pathway were altered prominently by QX1 formula treatment in the hippocampus of septic mice. In addition, QX1 formula administration decreased the expression of the M1 phenotype microglia gene markers such as Cd32, Socs3, and Cd68, while up-regulated M2 phenotype marker genes including Myc, Arg-1, and Cd206. Conclusions: QX1 formula administration attenuates cognitive deficits, emotional dysfunction, and reduces neuroinflammatory responses to improve survival in septic mice. Diminished microglial activation and altered microglial polarization are involved in the neuroprotective mechanism of QX1 formula.

scholarly journals AIM2 Inflammasome Mediates Hallmark Neuropathological Alterations and Cognitive Impairment in a Mouse Model of Vascular Dementia

2020 ◽  
Author(s):  
Luting Poh ◽  
David Y. Fann ◽  
Peiyan Wong ◽  
Hong Meng Lim ◽  
Sok Lin Foo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Model ◽  
Vascular Dementia ◽  
Cell Activation ◽  
Memory Loss ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Glial Cell Activation

AbstractChronic cerebral hypoperfusion is associated with vascular dementia (VaD). Cerebral hypoperfusion may initiate complex molecular and cellular inflammatory pathways that contribute to long-term cognitive impairment and memory loss. Here we used a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate its effect on the innate immune response – particularly the inflammasome signaling pathway. Comprehensive analyses revealed that chronic cerebral hypoperfusion induces a complex temporal expression and activation of inflammasome components and their downstream products (IL-1β and IL-18) in different brain regions, and promotes activation of apoptotic and pyroptotic cell death pathways. Polarized glial cell activation, white matter lesion formation and hippocampal neuronal loss also occurred in a spatiotemporal manner. Moreover, in AIM2 knockout mice we observed attenuated inflammasome-mediated production of proinflammatory cytokines, apoptosis and pyroptosis, as well as resistance to chronic microglial activation, myelin breakdown, hippocampal neuronal loss, and behavioural and cognitive deficits following BCAS. Hence, we have demonstrated that activation of the AIM2 inflammasome substantially contributes to the pathophysiology of chronic cerebral hypoperfusion-induced brain injury and may therefore represent a promising therapeutic target for attenuating cognitive impairment in VaD.

Immunogold labeling of the calcium binding protein synexin in isolated adrenal chromaffin granules and chromaffin cells

1990 ◽  
Vol 48 (3) ◽  
pp. 952-953
Author(s):  
Gemma A.J. Kuijpers ◽  
Harvey B. Pollard
Keyword(s):  
Adrenal Medulla ◽  
Calcium Binding ◽  
Chromaffin Cells ◽  
Cell Activation ◽  
Structural Information ◽  
Dependent Manner ◽  
Chromaffin Granules ◽  
Immuno Electron Microscopy ◽  
Ultrathin Sections ◽  
Adrenal Chromaffin

Exocytotic fusion of granules in the adrenal medulla chromaffin cell is triggered by a rise in the concentration of cytosolic Ca2+ upon cell activation. The protein synexin, annexin VII, was originally found in the adrenal medulla and has been shown to cause aggregation and to support fusion of chromaffin granules in a Ca2+-dependent manner. We have previously suggested that synexin may there fore play a role in the exocytotic fusion process. In order to obtain more structural information on synexin, we performed immuno-electron microscopy on frozen ultrathin sections of both isolated chromaffin granules and chromaffin cells.Chromaffin granules were isolated from bovine adrenal medulla, and synexin was isolated from bovine lung. Granules were incubated in the presence or absence of synexin (24 μg per mg granule protein) and Ca2+ (1 mM), which induces maximal granule aggregation, in 0.3M sucrose-40m MMES buffer(pH 6.0). Granules were pelleted, washed twice in buffer without synexin and fixed with 2% glutaraldehyde- 2% para formaldehyde in 0.1 M phosphate buffer (GA/PFA) for 30 min. Chromaffin cells were isolated and cultured for 3-5 days, and washed and incubated in Krebs solution with or without 20 uM nicotine. Cells were fixed 90 sec after on set of stimulation with GA/PFA for 30 min. Fixed granule or cell pellets were washed, infiltrated with 2.3 M sucrose in PBS, mounted and frozen in liquid N2.

“Subcortical” cognitive impairment in patients with systemic lupus erythematosus

2000 ◽  
Vol 6 (7) ◽  
pp. 821-825 ◽  
Author(s):  
ELIZABETH LERITZ ◽  
JASON BRANDT ◽  
MELISSA MINOR ◽  
FRANCES REIS-JENSEN ◽  
MICHELLE PETRI
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cognitive Impairment ◽  
Lupus Erythematosus ◽  
Systemic Lupus
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