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Find video protocols related to scientific articles indexed in Pubmed.
Chronic infection of Toxoplasma gondii downregulates miR-132 expression in multiple brain regions in a sex-dependent manner.
Parasitology
PUBLISHED: 10-30-2014
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SUMMARY MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions and its dysregulation is linked to several neurological disorders. We previously showed that acute Toxoplasma gondii infection induces miR-132 expression both in vitro and in vivo. To investigate the impact of chronic infection on miR-132, we infected mice with T. gondii PRU strain and performed assessment 5 months later in six brain regions (cortex, hypothalamus, striatum, cerebellum, olfactory bulb and hippocampus) by qPCR. We found that while acute infection of T. gondii increases the expression of miR-132, chronic infection has the opposite effect. The effect varied amongst different regions of the brain and presented in a sex-dependent manner, with females exhibiting more susceptibility than males. MiR-132 and brain-derived neurotrophic factor (BDNF, an inducer of miR-132) were not co-varies in the brain areas of infected mice. T. gondii DNA/RNA was found in all tested brain regions and a selective tropism towards the hippocampus, based on bradyzoite density, was observed in both males and females. However, the expressions of miR-132 or BDNF were poorly reflected by the density of T. gondii in brain areas. Our findings highlight the importance of investigating the miR-132-mediated neuronal function in mice infected with T. gondii.
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Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-27-2014
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Chloroviruses (family Phycodnaviridae) are large DNA viruses known to infect certain eukaryotic green algae and have not been previously shown to infect humans or to be part of the human virome. We unexpectedly found sequences homologous to the chlorovirus Acanthocystis turfacea chlorella virus 1 (ATCV-1) in a metagenomic analysis of DNA extracted from human oropharyngeal samples. These samples were obtained by throat swabs of adults without a psychiatric disorder or serious physical illness who were participating in a study that included measures of cognitive functioning. The presence of ATCV-1 DNA was confirmed by quantitative PCR with ATCV-1 DNA being documented in oropharyngeal samples obtained from 40 (43.5%) of 92 individuals. The presence of ATCV-1 DNA was not associated with demographic variables but was associated with a modest but statistically significant decrease in the performance on cognitive assessments of visual processing and visual motor speed. We further explored the effects of ATCV-1 in a mouse model. The inoculation of ATCV-1 into the intestinal tract of 9-11-wk-old mice resulted in a subsequent decrease in performance in several cognitive domains, including ones involving recognition memory and sensory-motor gating. ATCV-1 exposure in mice also resulted in the altered expression of genes within the hippocampus. These genes comprised pathways related to synaptic plasticity, learning, memory formation, and the immune response to viral exposure.
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One minute ultraviolet exposure inhibits Toxoplasma gondii tachyzoite replication and cyst conversion without diminishing host humoral-mediated immune response.
Exp. Parasitol.
PUBLISHED: 08-14-2014
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We developed a protocol to inactivate Toxoplasma gondii (T. gondii) tachyzoites employing 1 min of ultraviolet (UV) exposure. We show that this treatment completely inhibited parasite replication and cyst formation in vitro and in vivo but did not affect the induction of a robust IgG response in mice. We propose that our protocol can be used to study the contribution of the humoral immune response to rodent behavioral alterations following T. gondii infection.
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Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity.
Hum. Mol. Genet.
PUBLISHED: 07-04-2014
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Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. Disease pathogenesis derives, at least in part, from the long polyglutamine tract encoded by mutant HTT. Therefore, considerable effort has been dedicated to the development of therapeutic strategies that significantly reduce the expression of the mutant HTT protein. Antisense oligonucleotides (ASOs) targeted to the CAG repeat region of HTT transcripts have been of particular interest due to their potential capacity to discriminate between normal and mutant HTT transcripts. Here, we focus on phosphorodiamidate morpholino oligomers (PMOs), ASOs that are especially stable, highly soluble and non-toxic. We designed three PMOs to selectively target expanded CAG repeat tracts (CTG22, CTG25 and CTG28), and two PMOs to selectively target sequences flanking the HTT CAG repeat (HTTex1a and HTTex1b). In HD patient-derived fibroblasts with expanded alleles containing 44, 77 or 109 CAG repeats, HTTex1a and HTTex1b were effective in suppressing the expression of mutant and non-mutant transcripts. CTGn PMOs also suppressed HTT expression, with the extent of suppression and the specificity for mutant transcripts dependent on the length of the targeted CAG repeat and on the CTG repeat length and concentration of the PMO. PMO CTG25 reduced HTT-induced cytotoxicity in vitro and suppressed mutant HTT expression in vivo in the N171-82Q transgenic mouse model. Finally, CTG28 reduced mutant HTT expression and improved the phenotype of Hdh(Q7/Q150) knock-in HD mice. These data demonstrate the potential of PMOs as an approach to suppressing the expression of mutant HTT.
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Mouse models of gene-environment interactions in schizophrenia.
Neurobiol. Dis.
PUBLISHED: 05-10-2013
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Gene-environment interactions (GEIs) likely play significant roles in the pathogenesis of schizophrenia and underlie differences in pathological, behavioral, and clinical presentations of the disease. Findings from epidemiology and psychiatric genetics have assisted in the generation of animal models of GEI relevant to schizophrenia. These models may provide a foundation for elucidating the molecular, cellular, and circuitry mechanisms that mediate GEI in schizophrenia. Here we critically review current mouse models of GEI related to schizophrenia, describe directions for their improvement, and propose endophenotypes to provide a more tangible basis for molecular studies of pathways of GEI and facilitate the identification of novel therapeutic targets.
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Mutant DISC1 affects methamphetamine-induced sensitization and conditioned place preference: a comorbidity model.
Neuropharmacology
PUBLISHED: 02-01-2011
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Genetic factors involved in neuroplasticity have been implicated in major psychiatric illnesses such as schizophrenia, depression, and substance abuse. Given its extended interactome, variants in the Disrupted-In-Schizophrenia-1 (DISC1) gene could contribute to drug addiction and psychiatric diseases. Thus, we evaluated how dominant-negative mutant DISC1 influenced the neurobehavioral and molecular effects of methamphetamine (METH). Control and mutant DISC1 mice were studied before or after treatment with non-toxic escalating dose (ED) of METH. In naïve mice, we assessed METH-induced conditioned place preference (CPP), dopamine (DA) D2 receptor density and the basal and METH-induced activity of DISC1 partners, AKT and GSK-3? in the ventral striatum. In ED-treated mice, 4 weeks after METH treatment, we evaluated fear conditioning, depression-like responses in forced swim test, and the basal and METH-induced activity of AKT and GSK-3? in the ventral striatum. We found impairment in METH-induced CPP, decreased DA D2 receptor density and altered METH-induced phosphorylation of AKT and GSK-3? in naïve DISC1 female mice. The ED regimen was not neurotoxic as evidenced by unaltered brain regional monoamine tissue content. Mutant DISC1 significantly delayed METH ED-produced sensitization and affected drug-induced phosphorylation of AKT and GSK-3? in female mice. Our results suggest that perturbations in DISC1 functions in the ventral striatum may impact the molecular mechanisms of reward and sensitization, contributing to comorbidity between drug abuse and major mental diseases.
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Toxoplasma gondii strain-dependent effects on mouse behaviour.
Folia Parasitol.
PUBLISHED: 07-09-2010
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Toxoplasma gondii reportedly manipulates rodent behaviour to increase transmission to its definitive feline host. We compared the effects of mouse infection by two Type II strains of T. gondii, Prugniaud (PRU) and ME49, on attraction to cat odour, locomotor activity, anxiety, sensorimotor gating, and spatial working and recognition memory 2 months post-infection (mpi). Attraction to cat odour was reassessed 7 mpi. At 2 mpi, mice infected with either strain exhibited significantly more attraction to cat odour than uninfected animals did, but only PRU-infected mice exhibited this behaviour 7 mpi. PRU-infected mice had significantly greater body weights and hyperactivity, while ME49-infected mice exhibited impaired spatial working memory. No differences in parasite antibody titres were seen between PRU- and ME49-infected mice. The present data suggest the effect of T. gondii infection on mouse behaviour is parasite strain-dependent.
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Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology.
Biol. Psychiatry
PUBLISHED: 02-15-2010
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Gene-environment interactions (GEI) are involved in the pathogenesis of mental diseases. We evaluated interaction between mutant human disrupted-in-schizophrenia 1 (mhDISC1) and maternal immune activation implicated in schizophrenia and mood disorders.
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Anti-gluten immune response following Toxoplasma gondii infection in mice.
PLoS ONE
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Gluten sensitivity may affect disease pathogenesis in a subset of individuals who have schizophrenia, bipolar disorder or autism. Exposure to Toxoplasma gondii is a known risk factor for the development of schizophrenia, presumably through a direct pathological effect of the parasite on brain and behavior. A co-association of antibodies to wheat gluten and to T. gondii in individuals with schizophrenia was recently uncovered, suggesting a coordinated gastrointestinal means by which T. gondii and dietary gluten might generate an immune response. Here, we evaluated the connection between these infectious- and food-based antigens in mouse models. BALB/c mice receiving a standard wheat-based rodent chow were infected with T. gondii via intraperitoneal, peroral and prenatal exposure methods. Significant increases in the levels of anti-gluten IgG were documented in all infected mice and in offspring from chronically infected dams compared to uninfected controls (repetitive measures ANOVAs, two-tailed t-tests, all p?0.00001). Activation of the complement system accompanied this immune response (p?0.002-0.00001). Perorally-infected females showed higher levels of anti-gluten IgG than males (p?0.009) indicating that T. gondii-generated gastrointestinal infection led to a significant anti-gluten immune response in a sex-dependent manner. These findings support a gastrointestinal basis by which two risk factors for schizophrenia, T. gondii infection and sensitivity to dietary gluten, might be connected to produce the immune activation that is becoming an increasingly recognized pathology of psychiatric disorders.
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The Toxoplasma MAG1 peptides induce sex-based humoral immune response in mice and distinguish active from chronic human infection.
Microbes Infect.
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To distinguish active from inactive/chronic infection in Toxoplasma gondii-seropositive individuals, we have developed an enzyme-linked immunosorbent assay (ELISA) using specific peptides derived from Toxoplasma matrix antigen MAG1. We used this assay to measure matrix specific antibodies and pilot studies with infected mice established the validity of two peptides. The immune response against MAG1 occurs in about 12 days postinfection and displays a sex difference later on in mouse model, with males producing higher antibody titers than females. Serum samples from 22 patients with clinical toxoplasmosis and from 26 patients with serological evidence of past exposure to Toxoplasma (more than one year infection history) were analyzed. Both MAG1 peptides detected antibodies significant frequently and robustly from active stage than from the chronic stage of toxoplasmosis. The results indicate that both MAG1 peptides may be used as a tool to differentiate active from inactive infection. It also may be considered in the design of potential vaccines in humans.
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Toxoplasma gondii and cognitive deficits in schizophrenia: an animal model perspective.
Schizophr Bull
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Cognitive deficits are a core feature of schizophrenia. Epidemiological evidence indicates that microbial pathogens may contribute to cognitive impairment in patients with schizophrenia. Exposure to Toxoplasma gondii (T. gondii) has been associated with cognitive deficits in humans. However, the mechanisms whereby the parasite impacts cognition remain poorly understood. Animal models of T. gondii infection may aid in elucidating the underpinnings of cognitive dysfunction. Here, we (1) overview the literature on the association of T. gondii infection and cognitive impairment, (2) critically analyze current rodent models of cognitive deficits resulting from T. gondii infection, and (3) explore possible mechanisms whereby the parasite may affect cognitive function.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.