scholarly journals Widespread labeling and genomic editing of the fetal central nervous system by in utero CRISPR AAV9-PHP.eB administration

Development ◽  
2020 ◽  
Vol 148 (2) ◽  
pp. dev195586
Author(s):  
Shuntong Hu ◽  
Tao Yang ◽  
Yu Wang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Neurodevelopmental Disorders ◽  
Genetic Manipulation ◽  
Gene Knockout ◽  
In Utero ◽  
Neural Cells ◽  
Genetic Intervention ◽  
Genomic Editing

ABSTRACTEfficient genetic manipulation in the developing central nervous system is crucial for investigating mechanisms of neurodevelopmental disorders and the development of promising therapeutics. Common approaches including transgenic mice and in utero electroporation, although powerful in many aspects, have their own limitations. In this study, we delivered vectors based on the AAV9.PHP.eB pseudo-type to the fetal mouse brain, and achieved widespread and extensive transduction of neural cells. When AAV9.PHP.eB-coding gRNA targeting PogZ or Depdc5 was delivered to Cas9 transgenic mice, widespread gene knockout was also achieved at the whole brain level. Our studies provide a useful platform for studying brain development and devising genetic intervention for severe developmental diseases.

scholarly journals Flexible, fast and selective genetic manipulation of the vertebrate CNS with misPiggy

2018 ◽  
Author(s):  
Michal Slezak ◽  
Filip de Vin ◽  
Yohei Shinmyo ◽  
Mykhailo Y. Batiuk ◽  
Melvin Y. Rincon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Genetic Manipulation ◽  
Cell Types ◽  
In Utero ◽  
Cell Manipulation ◽  
Gain Of Function ◽  
Single Plasmid

AbstractIn utero electroporation is increasingly used for manipulation of gene expression in the mammalian central nervous system. Here we created a transposon-based single plasmid system, that allows long-term conditional loss- and gain-of-function experiments across major CNS cell types. The system is widely applicable across species, allowing fast, flexible and cheap cell manipulation in previously non-transgenic species.

Yoga Therapy on Cognitive Function in Neurodevelopmental Disorders

2020 ◽  
pp. 143-160
Author(s):  
Artchoudane Soccalingam ◽  
Meena Ramanathan ◽  
Ananda Balayogi Bhavanani
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Function ◽  
Neurodevelopmental Disorders ◽  
Body Awareness ◽  
Yoga Therapy ◽  
Breath Awareness ◽  
Major Factors ◽  
Sensory Processes ◽  
And Behavior

Neurodevelopmental disorders (NDDs) are birth imperfections that cause dysfunction in cognitive and sensory processes and impairment in motor function, communication, and behavior. The major factors responsible for increasing incidence of NDDs are genetic, psychosocial, and excessive use of drugs. Yoga alleviates neurological problems and NDDs. Asana is a physical movement with breath awareness that facilitates the development of body awareness, concentration, and memory and provides vital energy for children with neurodevelopmental disability. Yoga therapy improves sensory coordination and motor imitations that enable persons with cognitive disabilities to make meaningful response by the integration of senses and functions of central nervous system.

Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins

Cell ◽  
1994 ◽  
Vol 76 (1) ◽  
pp. 117-129 ◽  
Author(s):  
David Westaway ◽  
Stephen J. DeArmond ◽  
Juliana Cayetano-Canlas ◽  
Darlene Groth ◽  
Dallas Foster ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Peripheral Nerves ◽  
Prion Proteins ◽  
Wild Type ◽  
The Central Nervous System

scholarly journals Differential Effects of Three CanonicalToxoplasmaStrains on Gene Expression in Human Neuroepithelial Cells

2010 ◽  
Vol 79 (3) ◽  
pp. 1363-1373 ◽  
Author(s):  
Jianchun Xiao ◽  
Lorraine Jones-Brando ◽  
C. Conover Talbot ◽  
Robert H. Yolken
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Nucleotide Metabolism ◽  
Neural Cells ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Neuroepithelial Cells ◽  
The Central Nervous System

ABSTRACTStrain type is one of the key factors suspected to play a role in determining the outcome ofToxoplasmainfection. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to representative strains ofToxoplasmaby using microarray analysis to characterize the strain-specific host cell response. The study of neural cells is of interest in light of the ability ofToxoplasmato infect the brain and to establish persistent infection within the central nervous system. We found that the extents of the expression changes varied considerably among the three strains. Neuroepithelial cells infected withToxoplasmatype I exhibited the highest level of differential gene expression, whereas type II-infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to the central nervous system, while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter the expression of a clearly defined set of genes. Moreover, Ingenuity Pathways Analysis (IPA) suggests that the three lineages differ in the ability to manipulate their host; e.g., they employ different strategies to avoid, deflect, or subvert host defense mechanisms. These observed differences may explain some of the variation in the neurobiological effects of different strains ofToxoplasmaon infected individuals.

scholarly journals Borna Disease Virus Accelerates Inflammation and Disease Associated with Transgenic Expression of Interleukin-12 in the Central Nervous System

2002 ◽  
Vol 76 (23) ◽  
pp. 12223-12232 ◽  
Author(s):  
Susanna Freude ◽  
Jürgen Hausmann ◽  
Markus Hofer ◽  
Ngan Pham-Mitchell ◽  
Iain L. Campbell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transgenic Mice ◽  
Disease Virus ◽  
Biologically Active ◽  
Interleukin 12 ◽  
Wild Type ◽  
Borna Disease Virus ◽  
The Central Nervous System ◽  
Borna Disease

ABSTRACT Targeted expression of biologically active interleukin-12 (IL-12) in astrocytes of the central nervous system (CNS) results in spontaneous neuroimmunological disease of aged mice. Borna disease virus (BDV) can readily multiply in the mouse CNS but does not trigger disease in most strains. Here we show that a large percentage of IL-12 transgenic mice developed severe ataxia within 5 to 10 weeks after infection with BDV. By contrast, no disease developed in mock-infected IL-12 transgenic and wild-type mice until 4 months of age. Neurological symptoms were rare in infected wild-type animals, and if they occurred, these were milder and appeared later. Histological analyses showed that the cerebellum of infected IL-12 transgenic mice, which is the brain region with strongest transgene expression, contained large numbers of CD4+ and CD8+ T cells as well as lower numbers of B cells, whereas other parts of the CNS showed only mild infiltration by lymphocytes. The cerebellum of diseased mice further showed severe astrogliosis, calcifications and signs of neurodegeneration. BDV antigen and nucleic acids were present in lower amounts in the inflamed cerebellum of infected transgenic mice than in the noninflamed cerebellum of infected wild-type littermates, suggesting that IL-12 or IL-12-induced cytokines exhibited antiviral activity. We propose that BDV infection accelerates the frequency by which immune cells such as lymphocytes and NK cells enter the CNS and then respond to IL-12 present in the local milieu causing disease. Our results illustrate that infection of the CNS with a virus that is benign in certain hosts can be harmful in such normally disease-resistant hosts if the tissue is unfavorably preconditioned by proinflammatory cytokines.

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