This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

Event: 191

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Neuronal dysfunction

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Explore in a Third Party Tool

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
neuron

Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
neuron death in response to oxidative stress		increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Lipocalin 2/Iron complex increases, Cognative dysfunction	KeyEvent	Young Jun Kim (send email)	Under development: Not open for comment. Do not cite
elavl3, sox10, mbp induced neuronal effects	KeyEvent	Donggon Yoo (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?

It is possible to use several markers of neuronal cytoskeleton (e.g. : neurofimanent proteins, NF-L, -M, -H), synapses (e.g.: synaptophysin), neurotransmitters or enzymes involved in neurotransmitter synthesis (e.g.: thyrosine hydroxylase) and look for changes at the mRNA level with quantitative RT-PCR and at the protein level, with immunoblotting (ex. thyrosine hydroxylase, NF-L,-M,-H), immunocytochemistry followed by a quantification, or by enzymatic assays (e.g.: choline acetyltransferase, glutamic acid decarboxylase). Genomic, proteomic and metabolomic approaches are also suitable for a non targeted approach. All these techniques are widely used, but for a recent description in the context of neurotoxicology and neuroinflammation, see Sandström et al., 2014, von Tobel et al., 2014, Monnet-Tschudi et al., 2000).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

References

List of the literature that was cited for this KE description. More help

Choi WS, Abel G, Klintworth H, Flavell RA, Xia Z (2010) JNK3 mediates paraquat- and rotenone-induced dopaminergic neuron death. J Neuropathol Exp Neurol 69: 511-520

Corvino V, Marchese E, Michetti F, Geloso MC (2013) Neuroprotective strategies in hippocampal neurodegeneration induced by the neurotoxicant trimethyltin. Neurochem Res 38: 240-253

Janigro D, Costa LG (1987) Effects of trimethyltin on granule cells excitability in the in vitro rat dentate gyrus. Neurotoxicol Teratol 9: 33-38

Klintworth H, Garden G, Xia Z (2009) Rotenone and paraquat do not directly activate microglia or induce inflammatory cytokine release. Neurosci Lett 462: 1-5

Monnet-Tschudi F, Zurich MG, Honegger P (1996) Comparison of the developmental effects of two mercury compounds on glial cells and neurons in aggregate cultures of rat telencephalon. Brain Res 741: 52-59

Monnet-Tschudi F, Zurich MG, Schilter B, Costa LG, Honegger P (2000) Maturation-dependent effects of chlorpyrifos and parathion and their oxygen analogs on acetylcholinesterase and neuronal and glial markers in aggregating brain cell cultures. Toxicol Appl Pharmacol 165: 175-183

Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308: 1314-1318

Sandström von Tobel, J., D. Zoia, et al. (2014a). "Immediate and delayed effects of subchronic Paraquat exposure during an early differentiation stage in 3D-rat brain cell cultures." Toxicol Lett. DOI : 10.1016/j.toxlet.2014.02.001

Sanfeliu C, Sebastia J, Cristofol R, Rodriguez-Farre E (2003) Neurotoxicity of organomercurial compounds. Neurotox Res 5: 283-305

Stansfield KH, Pilsner JR, Lu Q, Wright RO, Guilarte TR (2012) Dysregulation of BDNF-TrkB signaling in developing hippocampal neurons by Pb(2+): implications for an environmental basis of neurodevelopmental disorders. Toxicol Sci 127: 277-295

von Tobel, J. S., P. Antinori, et al. (2014b). "Repeated exposure to Ochratoxin A generates a neuroinflammatory response, characterized by neurodegenerative M1 microglial phenotype." Neurotoxicology 44C: 61-70.

Xanthos DN, Sandkühler J (2014). Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity. Nat Rev Neurosci. 2014 Jan;15(1):43-53.