Neurofunctional endpoints assessed in human neuroblastoma SH-SY5Y cells for estimation of acute systemic toxicity

Gustafsson, Helena; Runesson, Johan; Lundqvist, Jessica; Lindegren, Heléne; Axelsson, Viktoria; Forsby, Anna

doi:10.1016/j.taap.2010.02.018

Cited by 21 publications

(26 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hundreds of targets may be affected by neurotoxicants. Since it is not practical to develop one assay for every molecular initiating event (MIE), downstream key events (KE) corresponding to essential neuronal functions affected by several MIEs provide a more economic basis for in vitro neurotoxicity testing (Bal-Price et al 2008;Galofré et al 2010;Gustafsson et al 2010;de Groot et al 2013;Bal-Price et al 2015a, b).…”

Section: Common Endpoints Of Neurotoxicity Testingmentioning

confidence: 99%

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

Neurotoxicity and developmental neurotoxicity are important issues of chemical hazard assessment. Since the interpretation of animal data and their extrapolation to man is challenging, and the amount of substances with information gaps exceeds present animal testing capacities, there is a big demand for in vitro tests to provide initial information and to prioritize for further evaluation. During the last decade, many in vitro tests emerged. These are based on animal cells, human tumour cell lines, primary cells, immortalized cell lines, embryonic stem cells, or induced pluripotent stem cells. They differ in their read-outs and range from simple viability assays to complex functional endpoints such as neural crest cell migration. Monitoring of toxicological effects on differentiation often requires multiomics approaches, while the acute disturbance of neuronal functions may be analysed by assessing electrophysiological features. Extrapolation from in vitro data to humans requires a deep understanding of the test system biology, of the endpoints used, and of the applicability domains of the tests. Moreover, it is important that these be combined in the right way to assess toxicity. Therefore, knowledge on the advantages and disadvantages of all cellular platforms, endpoints, and analytical methods is essential when establishing in vitro test systems for different aspects of neurotoxicity. The elements of a test, and their evaluation, are discussed here in the context of comprehensive prediction of potential hazardous effects of a compound. We summarize the main cellular characteristics underlying neurotoxicity, present an overview of cellular platforms and read-out combinations assessing distinct parts of acute and developmental neurotoxicology, and highlight especially the use of stem cell-based test systems to close gaps in the available battery of tests.

show abstract

Section: Common Endpoints Of Neurotoxicity Testingmentioning

confidence: 99%

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…In zebrafish, it has been reported that ethanol causes abnormal development of motor neurons and muscle fibers [25]. The neurotoxic effect of lindane has also been well documented [26], [44] and chronic exposure of low dose lindane causes neurobehavioral, neurochemical, and electrophysiologrcal efects in rat brain [45].…”

Section: Discussionmentioning

confidence: 99%

“…While two of them, ethanol [25] and lindane [26], are widely considered to be neurotoxins at high dose, three are candidate neurotoxins: acetaminophen [27], [28], atenolol [29] and atrazine [30], [31], [32]. The last one, mefenamic acid, is considered to be neuroprotectant [33].…”

Section: Discussionmentioning

confidence: 99%

Fluorescent Transgenic Zebrafish Tg(nkx2.2a:mEGFP) Provides a Highly Sensitive Monitoring Tool for Neurotoxins

Zhang

Gong

2013

PLoS ONE

View full text Add to dashboard Cite

Previously a standard toxicological test termed as DarT (Danio rerio Teratogenic assay) using wild type zebrafish embryos has been established and it is widely applied in toxicological and chemical screenings. As an increasing number of fluorescent transgenic zebrafish lines with specific fluorescent protein expression specifically expressed in different organs and tissues, we envision that the fluorescent markers may provide more sensitive endpoints for monitoring chemical induced phenotypical changes. Here we employed Tg(nkx2.2a:mEGFP) transgenic zebrafish which have GFP expression in the central nervous system to investigate its potential for screening neurotoxic chemicals. Five potential neurotoxins (acetaminophen, atenolol, atrazine, ethanol and lindane) and one neuroprotectant (mefenamic acid) were tested. We found that the GFP-labeled ventral axons from trunk motoneurons, which were easily observed in live fry and measured for quantification, were a highly sensitive to all of the five neurotoxins and the length of axons was significantly reduced in fry which looked normal based on DarT endpoints at low concentrations of neurotoxins. Compared to the most sensitive endpoints of DarT, ventral axon marker could improve the detection limit of these neurotoxins by about 10 fold. In contrast, there was no improvement for detection of the mefenamic acid compared to all DarT endpoints. Thus, ventral axon lengths provide a convenient and measureable marker specifically for neurotoxins. Our study may open a new avenue to use other fluorescent transgenic zebrafish embryos/fry to develop sensitive and specific toxicological tests for different categories of chemicals.

show abstract

“…To passage the cells, 0.05% Trypsin/0.02% EDTA solution in PBS was applied for 5 min at 37 °C, 5% CO 2 . Differentiation of SH-SY5Y cells was performed with 1 μM RA in DMEM F12 (1:1) medium (1% N2, 1 IU/ml penicillin and 1 μg/ml streptomycin) [47]. The cells were plated at a density of 500 cells/mm 2 in black clear bottom 96-well plates in the culture medium overnight.…”

Section: Methodsmentioning

confidence: 99%

Comparison of neurons derived from mouse P19, rat PC12 and human SH-SY5Y cells in the assessment of chemical- and toxin-induced neurotoxicity

Popova

Karlsson

Jacobsson

2017

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

BackgroundExposure to chemicals might be toxic to the developing brain. There is a need for simple and robust in vitro cellular models for evaluation of chemical-induced neurotoxicity as a complement to traditional studies on animals. In this study, neuronally differentiated mouse embryonal carcinoma P19 cells (P19 neurons) were compared with human neuroblastoma SH-SY5Y cells and rat adrenal pheochromocytoma PC12 cells for their ability to detect toxicity of methylmercury (MeHg), okadaic acid and acrylamide.MethodsRetinoic acid-treated P19 and SH-SY5Y cells and nerve growth factor-stimulated PC12 cells, allowed to differentiate for 6 days, were exposed to MeHg, okadaic acid and acrylamide for 48 h. Cell survival and neurite outgrowth were assessed with the calcein-AM assay and fluorescence detection of antibodies against the cytoskeletal neuron-specific protein βIII-tubulin, respectively. The effects of glutathione (GSH) and the potent inhibitor of GSH synthesis buthionine sulfoximine (BSO) on the MeHg induced-toxicity were assessed using the PrestoBlue™ cell viability assay and the TMRE mitochondrial membrane potential assay.ResultsDifferentiated P19 cells developed the most extensive neuronal network among the three cell models and were the most sensitive neuronal model to detect neurotoxic effects of the test compounds. MeHg produced a concentration-dependent toxicity in differentiated P19 cells and SH-SY5Y cells, with statistically significant effects at concentrations from 0.1 μM in the P19 neurons and 1 μM in the SH-SY5Y cells. MeHg induced a decrease in the cellular metabolic activity and mitochondrial membrane potential (ΔΨm) in the differentiated P19 cells and SH-SY5Y cells, that were attenuated by GSH. Okadaic acid and acrylamide also showed statistically significant toxicity in the P19 neurons, but not in the SH-SY5Y cells or the P12 cells.ConclusionsP19 neurons are more sensitive to detect cytotoxicity of MeHg, okadaic acid and acrylamide than retinoic acid-differentiated SH-SY5Y cells and nerve growth factor-treated PC12 cells. P19 neurons are at least as sensitive as differentiated SH-SY5Y cells to detect the loss of mitochondrial membrane potential produced by MeHg and the protective effects of extracellular GSH on MeHg toxicity. P19 neurons may be a useful model to study neurotoxic effects of chemicals.

show abstract

Neurofunctional endpoints assessed in human neuroblastoma SH-SY5Y cells for estimation of acute systemic toxicity

Cited by 21 publications

References 29 publications

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

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

Fluorescent Transgenic Zebrafish Tg(nkx2.2a:mEGFP) Provides a Highly Sensitive Monitoring Tool for Neurotoxins

Comparison of neurons derived from mouse P19, rat PC12 and human SH-SY5Y cells in the assessment of chemical- and toxin-induced neurotoxicity

Contact Info

Product

Resources

About