scholarly journals Kinematic Locomotion Changes in C57BL/6 Mice Infected with Toxoplasma Strain ME49

2019 ◽  
Vol 7 (11) ◽  
pp. 573 ◽  
Author(s):  
María de la Luz Galván-Ramírez ◽  
Angel Gustavo Salas-Lais ◽  
Sergio Horacio Dueñas-Jiménez ◽  
Gerardo Mendizabal-Ruiz ◽  
Ramón Franco Topete ◽  
...  

Chronic infection with the intracellular parasite Toxoplasma gondii produces an accumulation of cysts in the brain and muscle, causing tissue damage. The cysts in the brain motor regions affect some kinematic locomotion parameters in the host. To localize the brain cysts from Toxoplasma gondii and study the changes in kinematic locomotion in C57BL/6 mice. Female adult C57BL/6 mice were infected orally with 30 ME-49 Toxoplasma gondii cysts. An uninfected group (n = 7) and two infected groups, examined 15 and 40 days postinfection, were used for this study. To evaluate kinematic locomotion, the mice were marked with indelible ink on the iliac crest, hip, knee, ankle, and phalangeal metatarsus of the left and right hindlimbs. At least three recordings were carried out to obtain videos of the left and right hindlimbs. Mice were video recorded at 90 fps at a resolution of 640 × 480 pixels while walking freely in a transparent Plexiglass tunnel. We measured the hindlimb pendular movement and the hindlimb transfer [linear displacement] curves for each step and evaluated them statistically with Fréchet dissimilarity tests. Afterward, the mice were sacrificed, and the brain, heart, skeletal muscle, lung, liver, and kidney were obtained. The different tissues were stained with hematoxylin and eosin for analysis with optical microscopy. Topographic localization of the cysts was made using bregma coordinates for the mouse brain. The cysts were distributed in several brain regions. In one mouse, cyst accumulation occurred in the hippocampus, coinciding with an alteration in foot displacement. The step length was different among the different studied groups.

2017 ◽  
Vol 1 (6) ◽  
pp. 563-572 ◽  
Author(s):  
Pierre-Mehdi Hammoudi ◽  
Dominique Soldati-Favre

Typically illustrating the ‘manipulation hypothesis’, Toxoplasma gondii is widely known to trigger sustainable behavioural changes during chronic infection of intermediate hosts to enhance transmission to its feline definitive hosts, ensuring survival and dissemination. During the chronic stage of infection in rodents, a variety of neurological dysfunctions have been unravelled and correlated with the loss of cat fear, among other phenotypic impacts. However, the underlying neurological alteration(s) driving these behavioural modifications is only partially understood, which makes it difficult to draw more than a correlation between T. gondii infection and changes in brain homeostasis. Moreover, it is barely known which among the brain regions governing fear and stress responses are preferentially affected during T. gondii infection. Studies aiming at an in-depth dissection of underlying molecular mechanisms occurring at the host and parasite levels will be discussed in this review. Addressing this reminiscent topic in the light of recent technical progress and new discoveries regarding fear response, olfaction and neuromodulator mechanisms could contribute to a better understanding of this complex host–parasite interaction.


2019 ◽  
Vol 116 (49) ◽  
pp. 24796-24807 ◽  
Author(s):  
Christine A. Schneider ◽  
Dario X. Figueroa Velez ◽  
Ricardo Azevedo ◽  
Evelyn M. Hoover ◽  
Cuong J. Tran ◽  
...  

Brain infection by the parasite Toxoplasma gondii in mice is thought to generate vulnerability to predation by mechanisms that remain elusive. Monocytes play a key role in host defense and inflammation and are critical for controlling T. gondii. However, the dynamic and regional relationship between brain-infiltrating monocytes and parasites is unknown. We report the mobilization of inflammatory (CCR2+Ly6Chi) and patrolling (CX3CR1+Ly6Clo) monocytes into the blood and brain during T. gondii infection of C57BL/6J and CCR2RFP/+CX3CR1GFP/+ mice. Longitudinal analysis of mice using 2-photon intravital imaging of the brain through cranial windows revealed that CCR2-RFP monocytes were recruited to the blood–brain barrier (BBB) within 2 wk of T. gondii infection, exhibited distinct rolling and crawling behavior, and accumulated within the vessel lumen before entering the parenchyma. Optical clearing of intact T. gondii-infected brains using iDISCO+ and light-sheet microscopy enabled global 3D detection of monocytes. Clusters of T. gondii and individual monocytes across the brain were identified using an automated cell segmentation pipeline, and monocytes were found to be significantly correlated with sites of T. gondii clusters. Computational alignment of brains to the Allen annotated reference atlas [E. S. Lein et al., Nature 445:168–176 (2007)] indicated a consistent pattern of monocyte infiltration during T. gondii infection to the olfactory tubercle, in contrast to LPS treatment of mice, which resulted in a diffuse distribution of monocytes across multiple brain regions. These data provide insights into the dynamics of monocyte recruitment to the BBB and the highly regionalized localization of monocytes in the brain during T. gondii CNS infection.


2012 ◽  
Vol 56 (4) ◽  
pp. 1762-1768 ◽  
Author(s):  
Wai Kit Chew ◽  
Ignacio Segarra ◽  
Stephen Ambu ◽  
Joon Wah Mak

ABSTRACTToxoplasma gondiiis a parasite that generates latent cysts in the brain; reactivation of these cysts may lead to fatal toxoplasmic encephalitis, for which treatment remains unsuccessful. We assessed spiramycin pharmacokinetics coadministered with metronidazole, the eradication of brain cysts and thein vitroreactivation. Male BALB/c mice were fed 1,000 tachyzoites orally to develop chronic toxoplasmosis. Four weeks later, infected mice underwent different treatments: (i) infected untreated mice (n= 9), which received vehicle only; (ii) a spiramycin-only group (n= 9), 400 mg/kg daily for 7 days; (iii) a metronidazole-only group (n= 9), 500 mg/kg daily for 7 days; and (iv) a combination group (n= 9), which received both spiramycin (400 mg/kg) and metronidazole (500 mg/kg) daily for 7 days. An uninfected control group (n= 10) was administered vehicle only. After treatment, the brain cysts were counted, brain homogenates were cultured in confluent Vero cells, and cysts and tachyzoites were counted after 1 week. Separately, pharmacokinetic profiles (plasma and brain) were assessed after a single dose of spiramycin (400 mg/kg), metronidazole (500 mg/kg), or both. Metronidazole treatment increased the brain spiramycin area under the concentration-time curve from 0 h to ∞ (AUC0–∞) by 67% without affecting its plasma disposition. Metronidazole plasma and brain AUC0–∞values were reduced 9 and 62%, respectively, after spiramycin coadministration. Enhanced spiramycin brain exposure after coadministration reduced brain cysts 15-fold (79 ± 23 for the combination treatment versus 1,198 ± 153 for the untreated control group [P< 0.05]) and 10-fold versus the spiramycin-only group (768 ± 125). Metronidazole alone showed no effect (1,028 ± 149). Tachyzoites were absent in the brain. Spiramycin reducedin vitroreactivation. Metronidazole increased spiramycin brain penetration, causing a significant reduction ofT. gondiibrain cysts, with potential clinical translatability for chronic toxoplasmosis treatment.


2008 ◽  
Vol 23 (4) ◽  
pp. 281-288 ◽  
Author(s):  
Jamila Andoh ◽  
Jean-Luc Martinot

AbstractRepetitive transcranial magnetic stimulation (rTMS) applied over brain regions responsible for language processing is used to curtail potentially auditory hallucinations in schizophrenia patients and to investigate the functional organisation of language-related areas. Variability of effects is, however, marked across studies and between subjects. Furthermore, the mechanisms of action of rTMS are poorly understood.Here, we reviewed different factors related to the structural and functional organisation of the brain that might influence rTMS-induced effects. Then, by analogy with aphasia studies, and the plastic-adaptive changes in both the left and right hemispheres following aphasia recovery, a hypothesis is proposed about rTMS mechanisms over language-related areas (e.g. Wernicke, Broca). We proposed that the local interference induced by rTMS in language-related areas might be analogous to aphasic stroke and might lead to a functional reorganisation in areas connected to the virtual lesion for language recovery.


Entropy ◽  
2020 ◽  
Vol 22 (4) ◽  
pp. 465
Author(s):  
Manuel Curado ◽  
Francisco Escolano ◽  
Miguel A. Lozano ◽  
Edwin R. Hancock

Alzheimer’s disease has been extensively studied using undirected graphs to represent the correlations of BOLD signals in different anatomical regions through functional magnetic resonance imaging (fMRI). However, there has been relatively little analysis of this kind of data using directed graphs, which potentially offer the potential to capture asymmetries in the interactions between different anatomical brain regions. The detection of these asymmetries is relevant to detect the disease in an early stage. For this reason, in this paper, we analyze data extracted from fMRI images using the net4Lap algorithm to infer a directed graph from the available BOLD signals, and then seek to determine asymmetries between the left and right hemispheres of the brain using a directed version of the Return Random Walk (RRW). Experimental evaluation of this method reveals that it leads to the identification of anatomical brain regions known to be implicated in the early development of Alzheimer’s disease in clinical studies.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Miroslav Andjelković ◽  
Bosiljka Tadić ◽  
Roderick Melnik

Abstract Higher-order connectivity in complex systems described by simplexes of different orders provides a geometry for simplex-based dynamical variables and interactions. Simplicial complexes that constitute a functional geometry of the human connectome can be crucial for the brain complex dynamics. In this context, the best-connected brain areas, designated as hub nodes, play a central role in supporting integrated brain function. Here, we study the structure of simplicial complexes attached to eight global hubs in the female and male connectomes and identify the core networks among the affected brain regions. These eight hubs (Putamen, Caudate, Hippocampus and Thalamus-Proper in the left and right cerebral hemisphere) are the highest-ranking according to their topological dimension, defined as the number of simplexes of all orders in which the node participates. Furthermore, we analyse the weight-dependent heterogeneity of simplexes. We demonstrate changes in the structure of identified core networks and topological entropy when the threshold weight is gradually increased. These results highlight the role of higher-order interactions in human brain networks and provide additional evidence for (dis)similarity between the female and male connectomes.


2020 ◽  
Author(s):  
Sanjeeva Srivast ◽  
Deeptarup Biswas ◽  
Sanjyot Shenoy ◽  
Chetanya Chetanya ◽  
Arunachalam Athithyan ◽  
...  

Abstract The human brain has always been a black box full of mysteries. Here we present one of the most comprehensive proteomics investigation of the brain, focusing on inter-hemispheric differences. An extensive mass spectrometry-based analysis of 19 brain regions from both left and right hemispheres measured more than 3300 proteins and 38700 peptides. This high-resolution data provides a comprehensive coverage of experimentally measured (non-hypothetical) proteins across various regions to characterize inter-hemispheric differences. We also tried to understand the brain proteins in terms of synapse analysis. The study has attempted to investigate the expression of neuroanatomical allied region and brain disorder protein markers in 19 region and sub-region of brain. Furthermore, we have developed the most comprehensive Brain Proteome Database, based on our, and publicly available curated data representing more than 9000 proteins (with isoforms) and around 90000 peptides at www.brainprot.org, which can aid in understanding the human brain’s complexity.


2021 ◽  
Author(s):  
Xinlei Yan ◽  
Wenying Han ◽  
Xindong Jin ◽  
Yufei Sun ◽  
Jialu Gao ◽  
...  

Abstract Toxoplasma gondii is a worldwide food-borne parasite that can infect almost all warm-blooded animals, including humans. To date, there are no effective drugs to prevent or eradicate T. gondii infection. Recent studies have shown that probiotics could influence the relationship between the microbiota and parasites in the host. Koumiss has been used to treat many diseases based on its probiotic diversity. Therefore, we explored the effect of koumiss on T. gondii infection via its effect on the host intestinal flora. BALB/c mice were infected with T. gondii and treated with PBS, koumiss and mares’ milk. Brain cysts were counted, and long-term changes in the microbiota and the effect of koumiss on gut flora were investigated with high-throughput sequencing technology. The results suggested that koumiss treatment significantly decreased the cyst counts in the brain (P < 0.05). Moreover, T. gondii infection changed the microbiota composition, and koumiss treatment increased the relative abundance of Lachnospiraceae and Akkermansia muciniphila, which were associated with preventing T. gondii infection. Moreover, koumiss could inhibit or ameliorate T. gondii infection by increasing the abundance of certain bacteria that control unique metabolic pathways. The study not only established a close interaction among the host, intracellular pathogens and intestinal flora but also provided a novel focus for drug development to prevent and eradicate T. gondii infection.


1999 ◽  
Vol 22 (5) ◽  
pp. 854-855
Author(s):  
Dahlia W. Zaidel

When circumscribed brain regions are damaged in humans, highly specific impairments in language, memory, problem solving, and cognition are observed. Neurosurgery such as “split brain” or hemispherectomy, for example, has shown that encompassing regions, the left and right cerebral hemispheres, each control human behavior in unique ways. Observations stretching over 100 years of patients with unilateral focal brain damage have revealed, without the theoretical benefits of “cognitive neuroscience” or “cognitive psychology,” that human behavior is indeed controlled by the brain and its neurons.


2021 ◽  
Author(s):  
Gang Liu ◽  
Jing Wang

<div><div> <p><a></a></p><div> <p><a></a><a><i>Objective. </i></a>Modeling the brain as a white box is vital for investigating the brain. However, the physical properties of the human brain are unclear. Therefore, BCI algorithms using EEG signals are generally a data-driven approach and generate a black- or gray-box model. This paper presents the first EEG-based BCI algorithm (EEGBCI using Gang neurons, EEGG) decomposing the brain into some simple components with physical meaning and integrating recognition and analysis of brain activity. </p> <p><i>Approach. </i>Independent and interactive components of neurons or brain regions can fully describe the brain. This paper constructed a relationship frame based on the independent and interactive compositions for intention recognition and analysis using a novel dendrite module of Gang neurons. A total of 4,906 EEG data of left- and right-hand motor imagery(MI) from 26 subjects were obtained from GigaDB. Firstly, this paper explored EEGG’s classification performance by cross-subject accuracy. Secondly, this paper transformed the trained EEGG model into a relation spectrum expressing independent and interactive components of brain regions. Then, the relation spectrum was verified using the known ERD/ERS phenomenon. Finally, this paper explored the previously unreachable further BCIbased analysis of the brain. </p> <p><i>Main results. </i>(1) EEGG was more robust than typical “CSP+” algorithms for the poorquality data. (2) The relation spectrum showed the known ERD/ERS phenomenon. (3) Interestingly, EEGG showed that interactive components between brain regions suppressed ERD/ERS effects on classification. This means that generating fine hand intention needs more centralized activation in the brain. </p> <p><i>Significance. </i>EEGG decomposed the biological EEG-intention system of this paper into the relation spectrum inheriting the Taylor series (<i>in analogy with the data-driven but human-readable Fourier transform and frequency spectrum</i>), which offers a novel frame for analysis of the brain.</p> </div> </div></div><div><p></p></div>


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