Neurite Degeneration in Differentiated Human Neuroblastoma Cells

Nordin-Andersson, Marika; Forsby, Anna; Heldring, Nina; DeJongh, Joost; Kjellstrand, Per; Walum, Erik

doi:10.1016/s0887-2333(98)00035-6

Cited by 26 publications

(11 citation statements)

References 15 publications

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“…Additionally, it is known that 1–10 mM of caffeine triggers calcium release from intracellular stores through a caffeine-sensitive ryanodine receptor, and such increase could lead to cell death in the central nervous system [50, 51]. Furthermore, calcium itself could directly activate caspases (e.g., caspase-3) or even proteases, having a role in the degeneration of neurofilaments [52–54]. In our study, 24-hour treatment with 2 mg/mL of caffeine significantly decreased the total cell number (Figure 11(a)) and induced typical morphological signs of decreased viability in vitro (Figure 11(b)(8)).…”

Section: Discussionmentioning

confidence: 99%

Major Components of Energy Drinks (Caffeine, Taurine, and Guarana) Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

Zeidán-Chuliá

Gelain

Kolling

et al. 2013

Oxidative Medicine and Cellular Longevity

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Scope. To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125–2 mg/mL), taurine (1–16 mg/mL), and guarana (3.125–50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5–50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or “antioxidative stress”), could be a cause of in vitro toxicity induced by these drugs.

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Section: Discussionmentioning

confidence: 99%

Major Components of Energy Drinks (Caffeine, Taurine, and Guarana) Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

Zeidán-Chuliá

Gelain

Kolling

et al. 2013

Oxidative Medicine and Cellular Longevity

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“…Due to this obvious sensitivity and the known vulnerability of the developing brain towards neurotoxins (Grandjean and Landrigan, 2006), DNT has been mentioned when in vitro tests methods are discussed that provide an understanding of the molecular/cellular mechanisms involved in neurotoxicity (Bal-Price et al, 2010a). One of the most promising readouts that have been proposed to measure neurotoxicity/developmental neurotoxicity is the inhibition of neurite outgrowth (Nordin-Andersson et al, 1998, Radio et al, 2008, Radio and Mundy, 2008), a hallmark of neuronal differentiation. Recently, it could has been shown that neurite outgrowth was significantly inhibited by methylmercury at 0.001 μM, a concentration far below the cytotoxic concentration (1 μM) of this neurotoxin in PC12 cells that have been used in this assay (Radio et al, 2010).…”

Section: The Nfa a New In Vitro Tool For The Assessment Of Neurotomentioning

confidence: 99%

Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts

et al. 2012

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The developing nervous system is particularly vulnerable to chemical insults. Exposure to chemicals can results in neurobehavioural alterations, and these have been be used as sensitive readouts to assess neurotoxicity in animals and man. Deconstructing neurobehaviour into relevant cellular and molecular components may allow for detection of specific neurotoxic effects in cell-based systems, which in turn may allow an easier examination of neurotoxic pathways and modes of actions and eventually inform the regulatory assessment of chemicals with potential developmental neurotoxicity. Here, current developments towards these goals are reviewed. Imaging genetics (CB) provides new insights into the neurobiological correlates of cognitive function that are being used to delineate neurotoxic mechanisms. The gaps between in vivo neurobehaviour and real-time in vitro measurements of neuronal function are being bridged by ex vivo measurements of synaptic plasticity (RW). An example of solvent neurotoxicity demonstrates how an in vivo neurological defect can be linked via the N-methyl-D-aspartate (NMDA)-glutamate receptor as a common target to in vitro readouts (AB). Axonal and dendritic morphology in vitro proved to be good correlates of neuronal connectivity and neurobehaviour in animals exposed to polychlorinated biphenyls and organophosphorus pesticides (PJL). Similarly, chemically-induced changes in neuronal morphology affected the formation of neuronal networks on structured surfaces. Such network formation may become an important readout for developmental neurotoxicity in vitro (CvT), especially when combined with human neurons derived from embryonic stem cells (ML). We envision that future in vitro test systems for developmental neurotoxicity will combine the above approaches with exposure information, and we suggest a strategy for test system development and cell-based risk assessment.

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“…This mode of action on GABAergic neurotransmis sion might be reflected in the increase of GABA evoked mean response amplitudes after incubation with 0.5 mM ACR and thus, the ESCNs might be a suitable in vitro system to follow up this in vivo observation of Shi et al (2012). Compared to previous in vitro studies investigating the effects of ACR on neurites (Hardelauf et al, 2011;Martenson et al, 1995;Nordin Andersson et al, 1998, 2003 as an indicator of structural neurotoxicity, ESCN as well as pCN appear to be more resistant to ACR. Using the neuroblastoma cell line SH SY5Y, Hardelauf et al (2011) reported that 1 mM ACR clearly compromised a network of neurites.…”

Section: Acr Impairs Neuronal Function After Short Term Exposurementioning

confidence: 90%

Acrylamide alters neurotransmitter induced calcium responses in murine ESC-derived and primary neurons

et al. 2014

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Neurite Degeneration in Differentiated Human Neuroblastoma Cells

Cited by 26 publications

References 15 publications

Major Components of Energy Drinks (Caffeine, Taurine, and Guarana) Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

Major Components of Energy Drinks (Caffeine, Taurine, and Guarana) Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts

Acrylamide alters neurotransmitter induced calcium responses in murine ESC-derived and primary neurons

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