3D spheroid, toxicity, harmane, essential tremor (ET)
Abstract :
[en] Neurotoxicity or neuroprotection studies are ideally based on animals; but such in vivo research is becoming less and less resorted to, due to 3Rs regulations (replacing, reducing and refining) implemented to reduce the number and suffering of research animals. In vitro models are then widely used to replicate certain aspects of neurotoxicity; these essentially consist in 2D models. However, pharmaco-toxicological assays based on such 2D cell cultures show important limitations that may partially account for the high rate of clinical trial failures observed in neurosciences; this is most probably linked to the limited ability of these models to mimic the in vivo cell environment. More recently, new models based on 3D cultures were introduced to improve the simulation of the living organ; their ability to predict toxicity has already been demonstrated and these models are expected to improve the biological activity screening tests. Although the implementation of 3D cultures remains a challenge, many tools have been developed to efficiently produce them, notably based on non-scaffold, solid scaffolds, natural or synthetic hydrogels, hanging drop in micropatterned or non-adherent surface plates and microfluidic devices. We developed reproducible model of 3D spheroids from embryonic mouse cortical neurons, using molded agarose micro-wells; this method seems particularly practical, being customizable, widely available and not requiring specific cell treatments or assay components different from 2D cultures, allowing easy transposition of routine protocols. This 3D neurosphere model mimics a neuronal microenvironment, allowing a fine study of neurodegenerative disorder pathologies and the effect of chemicals on the brain, for that we applied it to assess the neurotoxic effects of harmane a β-Carboline alkaloids (βCAs) incriminated in the pathogenesis of Essential tremor (ET), one of the most prevalent neurological diseases. This model opens novel opportunities, not only from a pathogenic point of view, but also from a therapeutical perspective.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Aro, Rania ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Chimie thérapeutique et Pharmacognosie
NACHTERGAEL, Amandine ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Chimie thérapeutique et Pharmacognosie
Ris, Laurence ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Neurosciences
Manto, Mario ; Université de Mons - UMONS > Faculté de Médecine et de Pharmacie > Service de Neurosciences
M136 - Chimie thérapeutique et Pharmacognosie M119 - Neurosciences
Research institute :
R550 - Institut des Sciences et Technologies de la Santé R100 - Institut des Biosciences
Funders :
This research is in part funded through a Fonds Medical pour la Recherche dans le Hainaut (FMRH) grant and a Kangaroo grant from the UMONS Health Institute.
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