This AOP is licensed under the 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.
AOP: 471
Title
A descriptive phrase which references both the Molecular Initiating Event and Adverse Outcome.It should take the form “MIE leading to AO”. For example, “Aromatase inhibition leading to reproductive dysfunction” where Aromatase inhibition is the MIE and reproductive dysfunction the AO. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE.
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Various neuronal effects induced by elavl3, sox10, and mbp
Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters.
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elavl3, sox10, mbp induced neuronal effects
The current version of the Developer's Handbook will be automatically populated into the Handbook Version field when a new AOP page is created.Authors have the option to switch to a newer (but not older) Handbook version any time thereafter.
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Handbook Version v2.5
Graphical Representation
A graphical representation of the AOP.This graphic should list all KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs.
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Point of Contact
The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section.
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Donggon Yoo
(email point of contact)
Contributors
Users with write access to the AOP page. Entries in this field are controlled by the Point of Contact.
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- Donggon Yoo
Coaches
This field is used to identify coaches who supported the development of the AOP.Each coach selected must be a registered author.
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OECD Information Table
Provides users with information concerning how actively the AOP page is being developed and whether it is part of the OECD Workplan and has been reviewed and/or endorsed. OECD Project: Assigned upon acceptance onto OECD workplan. This project ID is managed and updated (if needed) by the OECD. OECD Status: For AOPs included on the OECD workplan, ‘OECD status’ tracks the level of review/endorsement of the AOP . This designation is managed and updated by the OECD. Journal-format Article: The OECD is developing co-operation with Scientific Journals for the review and publication of AOPs, via the signature of a Memorandum of Understanding. When the scientific review of an AOP is conducted by these Journals, the journal review panel will review the content of the Wiki. In addition, the Journal may ask the AOP authors to develop a separate manuscript (i.e. Journal Format Article) using a format determined by the Journal for Journal publication. In that case, the journal review panel will be required to review both the Wiki content and the Journal Format Article. The Journal will publish the AOP reviewed through the Journal Format Article. OECD iLibrary published version: OECD iLibrary is the online library of the OECD. The version of the AOP that is published there has been endorsed by the OECD. The purpose of publication on iLibrary is to provide a stable version over time, i.e. the version which has been reviewed and revised based on the outcome of the review. AOPs are viewed as living documents and may continue to evolve on the AOP-Wiki after their OECD endorsement and publication.
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OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on July 24, 2024 15:03
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Increase, CNS Neural cell death | October 17, 2023 04:07 |
N/A, Neurodegeneration | February 23, 2021 05:07 |
Decrease, elavl3 | October 17, 2023 04:09 |
Decrease, sox10 | October 17, 2023 04:11 |
Decrease, mbp | October 17, 2023 04:13 |
Neuroinflammation | July 15, 2022 09:54 |
Decreased, Neuronal network function in adult brain | September 16, 2017 10:15 |
Acetylcholine accumulation in synapses | June 26, 2020 13:06 |
Acetylcholinesterase (AchE) Inhibition | April 29, 2020 17:21 |
Synaptic dysfunction | March 11, 2025 00:02 |
Impaired axonial transport | January 29, 2019 10:07 |
Sensory axonal peripheral neuropathy | January 29, 2019 10:08 |
Overactivation, NMDARs | July 14, 2024 11:45 |
Neurological disorder | June 15, 2023 04:43 |
Neuronal dysfunction | April 07, 2022 09:32 |
Degeneration of dopaminergic neurons of the nigrostriatal pathway | March 15, 2018 12:50 |
impaired, Learning and memory | December 03, 2016 16:37 |
Encephalitis | February 23, 2021 05:22 |
Loss of drebrin | April 03, 2025 21:27 |
Parkinsonian motor deficits | March 12, 2018 12:44 |
Disruption, neurotransmitter release | July 21, 2023 16:35 |
Increase, seizure | April 14, 2017 14:59 |
Increased, epilepsy | June 02, 2017 12:17 |
Increase, Mortality | October 26, 2020 05:18 |
Activation, Glutamate-gated chloride channels | September 16, 2017 10:16 |
Activated, presynaptic neuron 1 | June 02, 2017 11:29 |
Inhibition, Feeding | January 14, 2025 10:26 |
Decreased, Ionotropic GABA receptor chloride channel conductance | December 03, 2016 16:37 |
Increased, Inhibitory postsynaptic potential | September 16, 2017 10:16 |
Induction, Somatic muscle paralysis | September 16, 2017 10:16 |
Increased, Neuronal synaptic inhibition | September 16, 2017 10:16 |
Oxidative Stress | November 15, 2024 10:33 |
Increase, CNS Neural cell death leads to Decrease, elavl3 | October 17, 2023 04:10 |
Increase, CNS Neural cell death leads to Decrease, sox10 | October 17, 2023 04:11 |
Increase, CNS Neural cell death leads to Decrease, mbp | October 17, 2023 04:13 |
Decrease, elavl3 leads to N/A, Neurodegeneration | October 17, 2023 04:13 |
Decrease, sox10 leads to N/A, Neurodegeneration | October 17, 2023 04:14 |
Decrease, mbp leads to N/A, Neurodegeneration | October 17, 2023 04:14 |
Neuroinflammation leads to N/A, Neurodegeneration | February 23, 2021 05:47 |
Oxidative Stress leads to N/A, Neurodegeneration | July 23, 2024 22:10 |
Oxidative Stress leads to Decreased, Neuronal network function in adult brain | July 24, 2024 15:00 |
ACh Synaptic Accumulation leads to AchE Inhibition | December 03, 2016 16:37 |
AchE Inhibition leads to Increase, CNS Neural cell death | October 17, 2023 04:20 |
AchE Inhibition leads to Dysfunctional synapses | October 17, 2023 04:21 |
Dysfunctional synapses leads to Impaired axonial transport | October 17, 2023 04:22 |
Impaired axonial transport leads to Sensory axonal peripheral neuropathy | January 29, 2019 10:12 |
Sensory axonal peripheral neuropathy leads to Decreased, Neuronal network function in adult brain | October 17, 2023 04:23 |
Overactivation, NMDARs leads to AchE Inhibition | October 17, 2023 04:27 |
Overactivation, NMDARs leads to Decreased, Neuronal network function in adult brain | October 17, 2023 04:28 |
N/A, Neurodegeneration leads to Overactivation, NMDARs | October 17, 2023 04:33 |
Overactivation, NMDARs leads to Neuroinflammation | October 17, 2023 04:34 |
Decreased, Neuronal network function in adult brain leads to Neurological disorder | October 17, 2023 04:36 |
Neuronal dysfunction leads to Neurological disorder | June 15, 2023 04:45 |
Decreased, Neuronal network function in adult brain leads to Neuroinflammation | October 17, 2023 04:37 |
Neuroinflammation leads to Degeneration of dopaminergic neurons of the nigrostriatal pathway | August 25, 2017 08:54 |
N/A, Neurodegeneration leads to impaired, Learning and memory | October 17, 2023 04:41 |
Decreased, Neuronal network function in adult brain leads to impaired, Learning and memory | October 17, 2023 04:41 |
Degeneration of dopaminergic neurons of the nigrostriatal pathway leads to impaired, Learning and memory | October 17, 2023 04:42 |
N/A, Neurodegeneration leads to Encephalitis | February 23, 2021 06:04 |
Dysfunctional synapses leads to impaired, Learning and memory | October 17, 2023 04:48 |
Loss of drebrin leads to Dysfunctional synapses | April 04, 2025 01:41 |
impaired, Learning and memory leads to Parkinsonian motor deficits | October 17, 2023 04:50 |
Disruption, neurotransmitter release leads to impaired, Learning and memory | October 17, 2023 04:51 |
N/A, Neurodegeneration leads to Increase, seizure | October 17, 2023 04:52 |
Increase, seizure leads to Increased, epilepsy | April 14, 2017 15:36 |
Increased, epilepsy leads to Increase, Mortality | October 17, 2023 04:54 |
Parkinsonian motor deficits leads to Increase, Mortality | October 17, 2023 04:55 |
Activation, Glutamate-gated chloride channels leads to Overactivation, NMDARs | October 17, 2023 04:56 |
Activation, Glutamate-gated chloride channels leads to Increase, CNS Neural cell death | October 17, 2023 04:56 |
Activated, presynaptic neuron 1 leads to Activation, Glutamate-gated chloride channels | October 17, 2023 04:57 |
Inhibition, Feeding leads to Increase, Mortality | October 17, 2023 04:58 |
Activated, presynaptic neuron 1 leads to Decreased, Ionotropic GABA receptor chloride channel conductance | October 17, 2023 05:00 |
Increased, Inhibitory postsynaptic potential leads to Induction, Somatic muscle paralysis | December 03, 2016 16:38 |
Induction, Somatic muscle paralysis leads to Increased, Neuronal synaptic inhibition | October 17, 2023 05:05 |
Increased, Neuronal synaptic inhibition leads to Inhibition, Feeding | October 17, 2023 05:06 |
Abstract
A concise and informative summation of the AOP under development that can stand-alone from the AOP page. The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance.
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AOP Development Strategy
Context
Used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development.The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below.
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Strategy
Provides a description of the approaches to the identification, screening and quality assessment of the data relevant to identification of the key events and key event relationships included in the AOP or AOP network.This information is important as a basis to support the objective/envisaged application of the AOP by the regulatory community and to facilitate the reuse of its components. Suggested content includes a rationale for and description of the scope and focus of the data search and identification strategy/ies including the nature of preliminary scoping and/or expert input, the overall literature screening strategy and more focused literature surveys to identify additional information (including e.g., key search terms, databases and time period searched, any tools used).
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Summary of the AOP
This section is for information that describes the overall AOP.The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed.
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Events:
Molecular Initiating Events (MIE)
An MIE is a specialised KE that represents the beginning (point of interaction between a prototypical stressor and the biological system) of an AOP.
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Key Events (KE)
A measurable event within a specific biological level of organisation.
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Adverse Outcomes (AO)
An AO is a specialized KE that represents the end (an adverse outcome of regulatory significance) of an AOP.
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Type | Event ID | Title | Short name |
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MIE | 2195 | Increase, CNS Neural cell death | Increase, CNS Neural cell death |
KE | 352 | N/A, Neurodegeneration | N/A, Neurodegeneration |
KE | 2078 | Loss of drebrin | Loss of drebrin |
KE | 2150 | Neurological disorder | Neurological disorder |
KE | 2196 | Decrease, elavl3 | Decrease, elavl3 |
KE | 2197 | Decrease, sox10 | Decrease, sox10 |
KE | 2198 | Decrease, mbp | Decrease, mbp |
KE | 188 | Neuroinflammation | Neuroinflammation |
KE | 1392 | Oxidative Stress | Oxidative Stress |
KE | 618 | Decreased, Neuronal network function in adult brain | Decreased, Neuronal network function in adult brain |
KE | 10 | Acetylcholine accumulation in synapses | ACh Synaptic Accumulation |
KE | 12 | Acetylcholinesterase (AchE) Inhibition | AchE Inhibition |
KE | 1582 | Impaired axonial transport | Impaired axonial transport |
KE | 1583 | Sensory axonal peripheral neuropathy | Sensory axonal peripheral neuropathy |
KE | 388 | Overactivation, NMDARs | Overactivation, NMDARs |
KE | 191 | Neuronal dysfunction | Neuronal dysfunction |
KE | 890 | Degeneration of dopaminergic neurons of the nigrostriatal pathway | Degeneration of dopaminergic neurons of the nigrostriatal pathway |
KE | 1944 | Synaptic dysfunction | Dysfunctional synapses |
KE | 2151 | Disruption, neurotransmitter release | Disruption, neurotransmitter release |
KE | 1018 | Activation, Glutamate-gated chloride channels | Activation, Glutamate-gated chloride channels |
KE | 1349 | Activated, presynaptic neuron 1 | Activated, presynaptic neuron 1 |
KE | 1177 | Decreased, Ionotropic GABA receptor chloride channel conductance | Decreased, Ionotropic GABA receptor chloride channel conductance |
KE | 1012 | Increased, Inhibitory postsynaptic potential | Increased, Inhibitory postsynaptic potential |
KE | 1014 | Induction, Somatic muscle paralysis | Induction, Somatic muscle paralysis |
KE | 1015 | Increased, Neuronal synaptic inhibition | Increased, Neuronal synaptic inhibition |
AO | 637 | impaired, Learning and memory | impaired, Learning and memory |
AO | 1841 | Encephalitis | Encephalitis |
AO | 896 | Parkinsonian motor deficits | Parkinsonian motor deficits |
AO | 1348 | Increase, seizure | Increase, seizure |
AO | 1363 | Increased, epilepsy | Increased, epilepsy |
AO | 350 | Increase, Mortality | Increase, Mortality |
AO | 1016 | Inhibition, Feeding | Inhibition, Feeding |
Relationships Between Two Key Events (Including MIEs and AOs)
This table summarizes all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP.Each table entry acts as a link to the individual KER description page.
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Title | Adjacency | Evidence | Quantitative Understanding |
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Network View
This network graphic is automatically generated based on the information provided in the MIE(s), KEs, AO(s), KERs and Weight of Evidence (WoE) summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs.
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Prototypical Stressors
A structured data field that can be used to identify one or more “prototypical” stressors that act through this AOP. Prototypical stressors are stressors for which responses at multiple key events have been well documented.
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Life Stage Applicability
The life stage for which the AOP is known to be applicable.
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Taxonomic Applicability
Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected.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.
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Sex Applicability
The sex for which the AOP is known to be applicable.
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Overall Assessment of the AOP
Addressess the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and Weight of Evidence (WoE) for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment).
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Domain of Applicability
Addressess the relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context.
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Essentiality of the Key Events
The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently, evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence. The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs.
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Evidence Assessment
Addressess the biological plausibility, empirical support, and quantitative understanding from each KER in an AOP.
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Known Modulating Factors
Modulating factors (MFs) may alter the shape of the response-response function that describes the quantitative relationship between two KES, thus having an impact on the progression of the pathway or the severity of the AO.The evidence supporting the influence of various modulating factors is assembled within the individual KERs.
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Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
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Quantitative Understanding
Optional field to provide quantitative weight of evidence descriptors.
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Considerations for Potential Applications of the AOP (optional)
Addressess potential applications of an AOP to support regulatory decision-making.This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment.
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References
List of the literature that was cited for this AOP.
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