scholarly journals Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks

Biology Open ◽  
2013 ◽  
Vol 2 (6) ◽  
pp. 605-612 ◽  
Author(s):  
H. Kiiski ◽  
R. Aanismaa ◽  
J. Tenhunen ◽  
S. Hagman ◽  
L. Yla-Outinen ◽  
...  
2020 ◽  
Vol 8 ◽  
Author(s):  
Joshua Colm Price ◽  
Raquel Mesquita-Ribeiro ◽  
Federico Dajas-Bailador ◽  
Melissa Louise Mather

2020 ◽  
Vol 10 (4) ◽  
pp. 215
Author(s):  
Tuyana Malankhanova ◽  
Lyubov Suldina ◽  
Elena Grigor’eva ◽  
Sergey Medvedev ◽  
Julia Minina ◽  
...  

Huntington’s disease (HD) is a severe neurodegenerative disorder caused by a CAG triplet expansion in the first exon of the HTT gene. Here we report the introduction of an HD mutation into the genome of healthy human embryonic fibroblasts through CRISPR/Cas9-mediated homologous recombination. We verified the specificity of the created HTT-editing system and confirmed the absence of undesirable genomic modifications at off-target sites. We showed that both mutant and control isogenic induced pluripotent stem cells (iPSCs) derived by reprogramming of the fibroblast clones can be differentiated into striatal medium spiny neurons. We next demonstrated phenotypic abnormalities in the mutant iPSC-derived neural cells, including impaired neural rosette formation and increased sensitivity to growth factor withdrawal. Moreover, using electron microscopic analysis, we detected a series of ultrastructural defects in the mutant neurons, which did not contain huntingtin aggregates, suggesting that these defects appear early in HD development. Thus, our study describes creation of a new isogenic iPSC-based cell system that models HD and recapitulates HD-specific disturbances in the mutant cells, including some ultrastructural features implemented for the first time.


Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 830
Author(s):  
Wataru Minoshima ◽  
Kyoko Masui ◽  
Tomomi Tani ◽  
Yasunori Nawa ◽  
Satoshi Fujita ◽  
...  

The excitatory synaptic transmission is mediated by glutamate (GLU) in neuronal networks of the mammalian brain. In addition to the synaptic GLU, extra-synaptic GLU is known to modulate the neuronal activity. In neuronal networks, GLU uptake is an important role of neurons and glial cells for lowering the concentration of extracellular GLU and to avoid the excitotoxicity. Monitoring the spatial distribution of intracellular GLU is important to study the uptake of GLU, but the approach has been hampered by the absence of appropriate GLU analogs that report the localization of GLU. Deuterium-labeled glutamate (GLU-D) is a promising tracer for monitoring the intracellular concentration of glutamate, but physiological properties of GLU-D have not been studied. Here we study the effects of extracellular GLU-D for the neuronal activity by using primary cultured rat hippocampal neurons that form neuronal networks on microelectrode array. The frequency of firing in the spontaneous activity of neurons increased with the increasing concentration of extracellular GLU-D. The frequency of synchronized burst activity in neurons increased similarly as we observed in the spontaneous activity. These changes of the neuronal activity with extracellular GLU-D were suppressed by antagonists of glutamate receptors. These results suggest that GLU-D can be used as an analog of GLU with equivalent effects for facilitating the neuronal activity. We anticipate GLU-D developing as a promising analog of GLU for studying the dynamics of glutamate during neuronal activity.


2001 ◽  
Vol 32 (5) ◽  
pp. 511-528 ◽  
Author(s):  
J. Waterhouse ◽  
A. Nevill ◽  
D. Weinert ◽  
S. Folkard ◽  
D. Minors ◽  
...  

2019 ◽  
Vol 139 (5) ◽  
pp. 638-639
Author(s):  
Kenta Shimba ◽  
Yasuyoshi Urata ◽  
Kiyoshi Kotani ◽  
Yasuhiko Jimbo

2014 ◽  
Vol 64 (6) ◽  
pp. 421-431 ◽  
Author(s):  
Kazuki Okamoto ◽  
Tomoe Ishikawa ◽  
Reimi Abe ◽  
Daisuke Ishikawa ◽  
Chiaki Kobayashi ◽  
...  

PLoS ONE ◽  
2007 ◽  
Vol 2 (5) ◽  
pp. e439 ◽  
Author(s):  
Alberto Mazzoni ◽  
Frédéric D. Broccard ◽  
Elizabeth Garcia-Perez ◽  
Paolo Bonifazi ◽  
Maria Elisabetta Ruaro ◽  
...  

STEMedicine ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. e35 ◽  
Author(s):  
Diletta Pozzi

In the absence of external stimuli, the nervous system exhibits a spontaneous electrical activity whose functions are not fully understood, and that represents the background noise of brain operations. Spontaneous activity has been proven to arise not only in vivo, but in in vitro neuronal networks as well, following some stereotypical patterns that reproduce the time course of development of the mammalian nervous system. This review provides an overview of in vitro models for the study of spontaneous network activity, discussing their ability to reproduce in vivo - like dynamics and the main findings obtained with each particular model. While explanted brain slices are able to reproduce the neuronal oscillations typically observed in anaesthetized animals, dissociated cultures allow the use of patient-derived neurons and limit the number of animals used for sample preparation.


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