scholarly journals Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and its impact on neuron biology

Open Biology ◽  
2021 ◽  
Vol 11 (10) ◽  
Author(s):  
Thomas Mouveaux ◽  
Emmanuel Roger ◽  
Alioune Gueye ◽  
Fanny Eysert ◽  
Ludovic Huot ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Brain Cell ◽  
Parasite Infection ◽  
Brain Cells ◽  
Specific Response ◽  
Rna Seq ◽  
Cell Infection ◽  
The Brain

Toxoplasma gondii is a eukaryotic parasite that forms latent cysts in the brain of immunocompetent individuals. The latent parasite infection of the immune-privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons' long-term infection are unknown. It has long been known that T. gondii specifically differentiates into a latent form (bradyzoite) in neurons, but how the infected neuron responds to the infection remains to be elucidated. We have established a new in vitro model resulting in the production of mature bradyzoite cysts in brain cells. Using dual, host and parasite RNA-seq, we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal-specific pathways are strongly affected, with synapse signalling being particularly affected, especially glutamatergic synapse signalling. The establishment of this new in vitro model allows investigating both the dynamics of parasite differentiation and the specific response of neurons to long-term infection by this parasite.

scholarly journals Primary brain cell infection by Toxoplasma gondii reveals the extent and dynamics of parasite differentiation and impact on neuron biology.

2021 ◽  
Author(s):  
Thomas Mouveaux ◽  
Emmanuel Roger ◽  
Alioune Gueye ◽  
Fanny Eysert ◽  
Ludovic Huot ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
In Vitro Model ◽  
Brain Cell ◽  
Brain Cells ◽  
Specific Response ◽  
Cell Infection ◽  
Vitro Model ◽  
The Brain

Toxoplasma gondii is a eukaryotic parasite that form latent cyst in the brain of immunocompetent individuals. The latent parasites infection of the immune privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons long-term infection are unknown. It has long been known that T. gondii specifically differentiate into a latent form (bradyzoite) in neurons, but how the infected neuron is responding to the infection remain to be elucidated. We have established a new in vitro model resulting in the production of fully mature bradyzoites cysts in brain cells. Using dual, host and parasite, RNA-seq we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal specific pathways are strongly affected, with synapse signaling being particularly affected, especially glutamatergic synapse. The establishment of this new in vitro model allows to investigate both the dynamics of the parasite differentiation and the specific response of neurons to the long term infection by this parasite.

scholarly journals MODL-16. ABEMACICLIB, A SELECTIVE CDK4/6 INHIBITOR, RESTRICTS GROWTH OF PEDIATRIC GLIAL-LINEAGE TUMORS IN VITRO AND IN VIVO

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii414-iii414
Author(s):  
Muh-Lii Liang ◽  
Tsung-Han Hsieh ◽  
Tai-Tong Wong
Keyword(s):  
Dna Repair ◽  
Therapeutic Strategy ◽  
Target Genes ◽  
Rna Seq ◽  
Downstream Target ◽  
Rb Phosphorylation ◽  
Glial Lineage

Abstract BACKGROUND Glial-lineage tumors constitute a heterogeneous group of neoplasms, comprising gliomas, oligodendrogliomas, and ependymomas, which account for 40%–50% of all pediatric central nervous system tumors. Advances in modern neuro-oncological therapeutics are aimed at improving neoadjuvant chemotherapy and deferring radiotherapy because radiation exposure may cause long-term side effects on the developing brain in young children. Despite aggressive treatment, more than half the high-grade gliomas (pHGGs) and one-third of ependymomas exhibit recurrence within 2 years of initial treatment. METHODS By using integrated bioinformatics and through experimental validation, we found that at least one gene among CCND1, CDK4, and CDK6 was overexpressed in pHGGs and ependymomas. RESULTS The use of abemaciclib, a highly selective CDK4/6 inhibitor, effectively inhibited cell proliferation and reduced the expression of cell cycle–related and DNA repair–related gene expression, which was determined through RNA-seq analysis. The efficiency of abemaciclib was validated in vitro in pHGGs and ependymoma cells and in vivo by using subcutaneously implanted ependymoma cells from patient-derived xenograft (PDX) in mouse models. Abemaciclib demonstrated the suppression of RB phosphorylation, downstream target genes of E2F, G2M checkpoint, and DNA repair, resulting in tumor suppression. CONCLUSION Abemaciclib showed encouraging results in preclinical pediatric glial-lineage tumors models and represented a potential therapeutic strategy for treating challenging tumors in children.

scholarly journals Effect of Water and Ethanol Extracts from Hericium erinaceus Solid-State Fermented Wheat Product on the Protection and Repair of Brain Cells in Zebrafish Embryos

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3297
Author(s):  
Shun-Kuo Sun ◽  
Chun-Yi Ho ◽  
Wei-Yang Yen ◽  
Su-Der Chen
Keyword(s):  
Solid State ◽  
Brain Cell ◽  
Hot Water ◽  
Raw Material ◽  
Brain Cells ◽  
Zebrafish Embryos ◽  
Hericium Erinaceus ◽  
Water Extracts ◽  
The Brain ◽  
Wheat Product

Extracts from Hericium erinaceus can cause neural cells to produce nerve growth factor (NGF) and protect against neuron death. The objective of this study was to evaluate the effects of ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product on the brain cells of zebrafish embryos in both pre-dosing protection mode and post-dosing repair mode. The results showed that 1% ethanol could effectively promote zebrafish embryo brain cell death. Both 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product protected brain cells and significantly reduced the death of brain cells caused by 1% ethanol treatment in zebrafish. Moreover, the zebrafish embryos were immersed in 1% ethanol for 4 h to cause brain cell damage and were then transferred and soaked in the 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product to restore the brain cells damaged by the 1% ethanol. However, the 200 ppm extracts from the unfermented wheat medium had no protective and repairing effects. Moreover, 200 ppm of ethanol and water extracts from H. erinaceus fruiting body had less significant protective and restorative effects on the brain cells of zebrafish embryos. Both the ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product could protect and repair the brain cells of zebrafish embryos damaged by 1% ethanol. Therefore, it has great potential as a raw material for neuroprotective health product.

The use of siRNA as a pharmacological tool to assess a role for the transcription factor NF-IL6 in the brain under in vitro and in vivo conditions during LPS-induced inflammatory stimulation

2017 ◽  
Vol 28 (6) ◽  
Author(s):  
Jelena Damm ◽  
Joachim Roth ◽  
Rüdiger Gerstberger ◽  
Christoph Rummel
Keyword(s):  
Transcription Factor ◽  
Brain Cells ◽  
Nuclear Factor ◽  
Si Rna ◽  
The Brain ◽  
Deficient Mice ◽  
Transcription Factor Nuclear Factor

AbstractBackground:Studies with NF-IL6-deficient mice indicate that this transcription factor plays a dual role during systemic inflammation with pro- and anti-inflammatory capacities. Here, we aimed to characterize the role of NF-IL6 specifically within the brain.Methods:In this study, we tested the capacity of short interfering (si) RNA to silence the inflammatory transcription factor nuclear factor-interleukin 6 (NF-IL6) in brain cells underResults:In cells of a mixed neuronal and glial primary culture from the ratConclusions:This approach was, thus, not suitable to characterize the role NF-IL6 in the brain

scholarly journals Toxoplasma gondii injected neurons localize to the cortex and striatum and have altered firing

2021 ◽  
Author(s):  
Oscar A. Mendez ◽  
Emiliano Flores Machado ◽  
Jing Lu ◽  
Anita A. Koshy
Keyword(s):  
Toxoplasma Gondii ◽  
Single Neuron ◽  
Latent Infection ◽  
Ex Vivo ◽  
Medium Spiny Neurons ◽  
Patch Clamping ◽  
Spiny Neurons ◽  
The Brain ◽  
Mapping Program

AbstractToxoplasma gondii is an intracellular parasite that causes a long-term latent infection of neurons. Using a custom MATLAB-based mapping program in combination with a mouse model that allows us to permanently mark neurons injected with parasite proteins, we found that Toxoplasma-injected neurons (TINs) are heterogeneously distributed in the brain, primarily localizing to the cortex followed by the striatum. Using immunofluorescence co-localization assays, we determined that cortical TINs are commonly (>50%) excitatory neurons (FoxP2+) and that striatal TINs are often (>65%) medium spiny neurons (MSNs) (FoxP2+). As MSNs have highly characterized electrophysiology, we used ex vivo slices from infected mice to perform single neuron patch-clamping on striatal TINs and neighboring uninfected MSNs (bystander MSNs). These studies demonstrated that TINs have highly abnormal electrophysiology, while the electrophysiology of bystander MSNs was akin to that of MSNs from uninfected mice. Collectively, these data offer new neuroanatomic and electrophysiologic insights into CNS toxoplasmosis.

Cannabinoid effects on adenylate cyclase and phosphodiesterase activities of mouse brain

1977 ◽  
Vol 55 (4) ◽  
pp. 934-942 ◽  
Author(s):  
Thomas W. Dolby ◽  
Lewis J. Kleinsmith
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Mouse Brain ◽  
Biogenic Amine ◽  
Specific Activity ◽  
Intraperitoneal Administration ◽  
The Brain

The experiments presented in this paper examine the mechanisms underlying the ability of cannabinoids to alter the in vivo levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in mouse brain. It was found that changes in cyclic AMP levels are a composite result of direct actions of cannabinoids on adenylate cyclase (EC 4.6.1.1) activity and indirect actions involving the potentiation or inhibition of biogenic amine induced activity of adenylate cyclase. Furthermore, the long-term intraperitoneal administration of 1-(−)-Δ-tetrahydrocannabinol to mice produced a form of phosphodiesterase (EC 3.1.4.17) in the brain whose activity is not stimulated by Ca2+, although its basal specific activity is similar to that of control animals. In vitro, the presence of the cannabinoids caused no significant changes in activity of brain PDE at the concentrations tested. Some correlations are presented which imply that many of the observed behavioral and physiological actions of the cannabinoids in mammalian organisms may be mediated via cyclic AMP mechanisms.

The effect of L-carnitine depletion induced by long-term therapy of mice with meldonium on brain mitochondrial balance

2021 ◽  
Vol 67 (1) ◽  
pp. 74-80
Author(s):  
E.A. Shaforostova ◽  
A.P. Gureev ◽  
I.Yu. Vitkalova ◽  
V.N. Popov
Keyword(s):  
Mitochondrial Biogenesis ◽  
Term Therapy ◽  
Brain Cells ◽  
Oxygen Species ◽  
Mitochondrial Potential ◽  
Metabolic Drug ◽  
Negative Effect ◽  
Long Term Therapy ◽  
The Brain

Meldonium is a metabolic drug used for treatment of coronary heart disease. The effect of the drug lies in its ability to inhibit synthesis and transport of L-carnitine. At the same time, a long-term deficiency of L-carnitine can theoretically negatively affect the activity of the transcription factor Nrf2, which is extremely important for maintaining mitochondrial balance in cells. We have shown that meldonium therapy for 3 months at a dose of 100 mg/kg in mice causes a decrease in the expression of the Nrf2 gene in the brain. A decrease in the Nrf2 level causes suppression of mitochondrial biogenesis, which is manifested in a decrease in the level of mtDNA and the level of Cox1 expression. However, no negative effect of meldonium on the bioenergetics parameters of mitochondria was found, as evidenced by the maintenance of a stable mitochondrial potential and the level of production of reactive oxygen species. Jne mohth after the end of the meldonium therapy, expression of the genes responsible for mitochondrial biogenesis and mitophagy (p62, Pink1, Tfam) was observed and the expression level of genes responsible for mitochondrial fusion returned to control values. These changes may be associated with the normalization of the level of L-carnitine in brain cells.

scholarly journals Altered expression of DNA damage repair genes in the brain tissue of mice conceived by in vitro fertilization

2020 ◽  
Vol 26 (3) ◽  
pp. 141-153
Author(s):  
Minhao Hu ◽  
Yiyun Lou ◽  
Shuyuan Liu ◽  
Yuchan Mao ◽  
Fang Le ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Brain Tissue ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Gene And Protein Expression ◽  
The Brain ◽  
Repair Genes

Abstract Our previous study revealed a higher incidence of gene dynamic mutation in newborns conceived by IVF, highlighting that IVF may be disruptive to the DNA stability of IVF offspring. However, the underlying mechanisms remain unclear. The DNA damage repair system plays an essential role in gene dynamic mutation and neurodegenerative disease. To evaluate the long-term impact of IVF on DNA damage repair genes, we established an IVF mouse model and analyzed gene and protein expression levels of MSH2, MSH3, MSH6, MLH1, PMS2, OGG1, APEX1, XPA and RPA1 and also the amount of H2AX phosphorylation of serine 139 which is highly suggestive of DNA double-strand break (γH2AX expression level) in the brain tissue of IVF conceived mice and their DNA methylation status using quantitative real-time PCR, western blotting and pyrosequencing. Furthermore, we assessed the capacity of two specific non-physiological factors in IVF procedures during preimplantation development. The results demonstrated that the expression and methylation levels of some DNA damage repair genes in the brain tissue of IVF mice were significantly changed at 3 weeks, 10 weeks and 1.5 years of age, when compared with the in vivo control group. In support of mouse model findings, oxygen concentration of in vitro culture environment was shown to have the capacity to modulate gene expression and DNA methylation levels of some DNA damage repair genes. In summary, our study indicated that IVF could bring about long-term alterations of gene and protein expression and DNA methylation levels of some DNA damage repair genes in the brain tissue and these alterations might be resulted from the different oxygen concentration of culture environment, providing valuable perspectives to improve the safety and efficiency of IVF at early embryonic stage and also throughout different life stages.

Sera of long term responders to interferon contain neutralizing anti-HCV antibodies, identified through an in vitro biliary cell infection assay

2001 ◽  
Vol 34 ◽  
pp. 129-130
Author(s):  
S. Bichr ◽  
R. Rende-Fournier ◽  
E. Depla ◽  
G. Maertens ◽  
C. Brechot
Keyword(s):  
Cell Infection ◽  
Infection Assay

scholarly journals Rosuvastatin revert memory impairment and anxiogenic-like effect in mice infected with the chronic ME-49 strain of Toxoplasma gondii

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250079
Author(s):  
Fernanda Ferreira Evangelista ◽  
Willian Costa-Ferreira ◽  
Francini Martini Mantelo ◽  
Lucimara Fátima Beletini ◽  
Amanda Hinobu de Souza ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Memory Impairment ◽  
Brain Inflammation ◽  
Long Term Memory ◽  
Histopathological Analysis ◽  
Term Memory ◽  
Anxiogenic Effect ◽  
Short And Long Term ◽  
The Brain

The aim of this study was to investigate the effect of rosuvastatin treatment on memory impairment, and anxiogenic-like effects in mice chronically infected with Toxoplasma gondii. For this, Balb/c mice were infected orally with chronic ME-49 strain of Toxoplasma gondii. Oral treatment with rosuvastatin (40mg/kg/day) started on the 51st day post-infection and was performed daily for 21 days. After completion of treatment, anxiety-like effects and locomotion were investigated in the open field (OF) test, whereas novel object recognition (NOR) test was used for evaluation of short- and long-term memory. At the end of the experiments, the brain was collected for Toxoplasma gondii DNA quantification and histopathological analysis. Infection with ME-49 strain decreased the time spent in the center of OF, indicating an anxiogenic effect, without affecting total and peripheral locomotion. Rosuvastatin treatment inhibited the change in the center time. Besides, pharmacological treatment increased total and central locomotion in both non-infected and infected animals. Infection also impaired both short- and long-term memory in the NOR test, and these effects were reverted by rosuvastatin treatment. In addition to effects in behavioral changes, rosuvastatin also reduced parasite load in the brain and attenuated signs of brain inflammation such as perivascular cuffs, inflammatory cell infiltration and tissue damage. These findings indicate for the first time the efficacy of rosuvastatin in treatment of memory impairment and anxiogenic effect evoked by infection with Toxoplasma gondii. These effects might be mediated by reduced cyst load, which in turn decrease inflammation and damage in the brain.

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