NDLI: A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis

Content Provider	Springer Nature Link
Author	Smirva, L. Harris, G. Delp, J. Valadares, M. Pamies, D. Hogberg, H. T. Waldmann, T. Leist, M. Hartung, T.
Copyright Year	2015
Abstract	Several shortcomings of current Parkinson’s disease (PD) models limit progress in identification of environmental contributions to disease pathogenesis. The conditionally immortalized cell line LUHMES promises to make human dopaminergic neuronal cultures more easily available, but these cells are difficult to culture for extended periods of time. We overcame this problem by culturing them in 3D with minor medium modifications. The 3D neuronal aggregates allowed penetration by small molecules and sufficient oxygen and nutrient supply for survival of the innermost cells. Using confocal microscopy, gene expression, and flow cytometry, we characterized the 3D model and observed a highly reproducible differentiation process. Visualization and quantification of neurites in aggregates was achieved by adding 2 % red fluorescent protein-transfected LUHMES cells. The mitochondrial toxicants and established experimental PD agents, rotenone and MPP+, perturbed genes involved in one-carbon metabolism and transsulfuration pathways (ASS1, CTH, and SHTM2) as in 2D cultures. We showed, for the first time in LUHMES, down-regulation of mir-7, a miRNA known to target alpha-synuclein and to be involved in PD. This was observed as early as 12 h after rotenone exposure, when pro-apoptotic mir-16 and rotenone-sensitive mir-210 were not yet significantly perturbed. Finally, washout experiments demonstrated that withdrawal of rotenone led to counter-regulation of mir-7 and ASS1, CTH, and SHTM2 genes. This suggests a possible role of these genes in direct cellular response to the toxicant, and the model appears to be suitable to address the processes of resilience and recovery in neurotoxicology and Parkinson’s disease in future studies.
Starting Page	2725
Ending Page	2743
Page Count	19
File Format	PDF
ISSN	03405761
Journal	Archives of Toxicology
Volume Number	90
Issue Number	11
e-ISSN	14320738
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2015-12-08
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	3D culture Neurotoxicity Resilience microRNA Rotenone Pharmacology/Toxicology Occupational Medicine/Industrial Medicine Environmental Health Biomedicine
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis

Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model exposed to rotenone

Perfluorooctane sulfonate induces neuronal vulnerability by decreasing GluR2 expression

In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities

Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation

Comparative analysis of 3D culture methods on human HepG2 cells

Bilirubin-induced ER stress contributes to the inflammatory response and apoptosis in neuronal cells

Acute and long-term in vitro effects of zinc oxide nanoparticles

A novel regulatory network among LncRpa, CircRar1, MiR-671 and apoptotic genes promotes lead-induced neuronal cell apoptosis

A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis

Similar Documents

A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis

Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model exposed to rotenone

Perfluorooctane sulfonate induces neuronal vulnerability by decreasing GluR2 expression

In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities

Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation

Comparative analysis of 3D culture methods on human HepG2 cells

Bilirubin-induced ER stress contributes to the inflammatory response and apoptosis in neuronal cells

Acute and long-term in vitro effects of zinc oxide nanoparticles

A novel regulatory network among LncRpa, CircRar1, MiR-671 and apoptotic genes promotes lead-induced neuronal cell apoptosis

A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis