scholarly journals Integration of human model neurons (NT2) into embryonic chick nervous system

2009 ◽  
Vol 239 (2) ◽  
pp. 496-504 ◽  
Author(s):  
Grzegorz Podrygajlo ◽  
Christoph Wiegreffe ◽  
Martin Scaal ◽  
Gerd Bicker
2007 ◽  
Vol 12 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Andrea M. Stahl ◽  
Gordon Ruthel ◽  
Edna Torres-Melendez ◽  
Tara A. Kenny ◽  
Rekha G. Panchal ◽  
...  

Botulinum toxin is an exceedingly potent inhibitor of neurotransmission across the neuromuscular junction, causing flaccid paralysis and death. The potential for misuse of this deadly poison as a bioweapon has added a greater urgency to the search for effective therapeutics. The development of sensitive and efficient cell-based assays for the evaluation of toxin antagonists is crucial to the rapid and successful identification of therapeutic compounds. The authors evaluated the sensitivity of primary cultures from 4 distinct regions of the embryonic chick nervous system to botulinum neurotoxin A (BoNT/A) cleavage of synaptosomal-associated protein of 25 kD (SNAP-25). Although differences in sensitivity were apparent, SNAP-25 cleavage was detectable in neuronal cells from each of the 4 regions within 3 h at BoNT/A concentrations of 1 nM or lower. Co-incubation of chick neurons with BoNT/A and toxin-neutralizing antibodies inhibited SNAP-25 cleavage, demonstrating the utility of these cultures for the assay of BoNT/A antagonists. ( Journal of Biomolecular Screening 2007:370-377)


1997 ◽  
Vol 17 (14) ◽  
pp. 5466-5479 ◽  
Author(s):  
A. John MacLennan ◽  
Diana L. McLaurin ◽  
Lianne Marks ◽  
Emily N. Vinson ◽  
Marylynn Pfeifer ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Thiago Arzua ◽  
Yasheng Yan ◽  
Congshan Jiang ◽  
Sarah Logan ◽  
Reilly L. Allison ◽  
...  

Abstract Maternal alcohol exposure during pregnancy can substantially impact the development of the fetus, causing a range of symptoms, known as fetal alcohol spectrum disorders (FASDs), such as cognitive dysfunction and psychiatric disorders, with the pathophysiology and mechanisms largely unknown. Recently developed human cerebral organoids from induced pluripotent stem cells are similar to fetal brains in the aspects of development and structure. These models allow more relevant in vitro systems to be developed for studying FASDs than animal models. Modeling binge drinking using human cerebral organoids, we sought to quantify the downstream toxic effects of alcohol (ethanol) on neural pathology phenotypes and signaling pathways within the organoids. The results revealed that alcohol exposure resulted in unhealthy organoids at cellular, subcellular, bioenergetic metabolism, and gene expression levels. Alcohol induced apoptosis on organoids. The apoptotic effects of alcohol on the organoids depended on the alcohol concentration and varied between cell types. Specifically, neurons were more vulnerable to alcohol-induced apoptosis than astrocytes. The alcohol-treated organoids exhibit ultrastructural changes such as disruption of mitochondria cristae, decreased intensity of mitochondrial matrix, and disorganized cytoskeleton. Alcohol exposure also resulted in mitochondrial dysfunction and metabolic stress in the organoids as evidenced by (1) decreased mitochondrial oxygen consumption rates being linked to basal respiration, ATP production, proton leak, maximal respiration and spare respiratory capacity, and (2) increase of non-mitochondrial respiration in alcohol-treated organoids compared with control groups. Furthermore, we found that alcohol treatment affected the expression of 199 genes out of 17,195 genes analyzed. Bioinformatic analyses showed the association of these dysregulated genes with 37 pathways related to clinically relevant pathologies such as psychiatric disorders, behavior, nervous system development and function, organismal injury and abnormalities, and cellular development. Notably, 187 of these genes are critically involved in neurodevelopment, and/or implicated in nervous system physiology and neurodegeneration. Furthermore, the identified genes are key regulators of multiple pathways linked in networks. This study extends for the first time animal models of binge drinking-related FASDs to a human model, allowing in-depth analyses of neurotoxicity at tissue, cellular, subcellular, metabolism, and gene levels. Hereby, we provide novel insights into alcohol-induced pathologic phenotypes, cell type-specific vulnerability, and affected signaling pathways and molecular networks, that can contribute to a better understanding of the developmental neurotoxic effects of binge drinking during pregnancy.


Neuron ◽  
1995 ◽  
Vol 14 (6) ◽  
pp. 1131-1140 ◽  
Author(s):  
Yuling Luo ◽  
Iain Shepherd ◽  
Jie Li ◽  
Michael J Renzi ◽  
Susannah Chang ◽  
...  

1975 ◽  
Vol 53 (6) ◽  
pp. 1005-1006 ◽  
Author(s):  
J. Lelorier ◽  
N. Minejima ◽  
F. E. Shideman

Attempts to assess the importance of the role played by endogenous catecholamines in the positive inotropic response to ouabain have produced contradictory results. The sympathetic nervous system is not present in the 4-day-old chicken embryo heart but is fully developed after 7 days of embryonic life. This was confirmed by the fact 4-day-old hearts do not respond to tyramine and cocaine while the usual positive inotropic and chronotropic responses were observed when these drugs were administered to 7-day-old hearts. In spite of this difference the positive inotropic response to ouabain was virtually identical at these two stages of development.


FEBS Letters ◽  
1999 ◽  
Vol 461 (1-2) ◽  
pp. 86-90 ◽  
Author(s):  
Jeanette C. Perron ◽  
John L. Bixby

1997 ◽  
Vol 1 (4) ◽  
pp. 344-346 ◽  
Author(s):  
Hubert Monnerie ◽  
Odile Boespflug-Tanguy ◽  
Bernard Dastugue ◽  
Annie Meiniel

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