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Event: 2242

Key Event Title

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

Abnormality, dendritic spine morphology

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

Dendritic spine abnormality

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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

Organ term
brain

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
negative regulation of synaptic plasticity	postsynaptic actin cytoskeleton	pathological
Dementia	drebrin	decreased
long term synaptic depression	drebrin	decreased
abnormal long term potentiation	drebrin	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
IGR binding leads to impairment of learning and memory (via loss of drebrin)	KeyEvent	Shihori Tanabe (send email)	Under development: Not open for comment. Do not cite	Under Development

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

Term	Scientific Term	Evidence	Link
Human, rat, mouse	Human, rat, mouse	High	NCBI

Life Stages

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

Life stage	Evidence
During brain development, adulthood and aging	High

Sex Applicability

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

Term	Evidence
Unspecific	High

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

Abnormalities in dendritic spines have been implicated in a wide range of psychiatric and neurological disorders, with initial discoveries stemming from Golgi staining of postmortem brains. These spine pathologies have been observed across various conditions, including schizophrenia, autism spectrum disorders (ASD), Alzheimer's disease (AD), bipolar disorder, Down syndrome, and epilepsy.　Alzheimer's disease brains exhibit reduced synapse density and dendritic spine loss in the cortex and hippocampus, with greater spine loss associated with lower mental status　This synaptic pathology is considered one of the earliest features of AD, occurring prior to neuronal loss. The shared feature of spine pathology across these disorders suggests that dendritic spines may serve as a common substrate for many brain disorders involving deficits in information processing and neuronal connectivity.

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

Drebrin immunocytochemistry can be used to measure the number of drebrin clusters.

Domain of Applicability

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

This KE applies to mammals of both sexes, during neuronal development at any life stage (both immature and adult nervous system).

References

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

Results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).

Search: Dendritic Spine abnormality

Marin-Padilla M. Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome. A Golgi study. J Comp Neurol. 1976 May 1;167(1):63-81. doi: 10.1002/cne.901670105. PMID: 131810.

Gonatas NK, Moss A. Pathologic axons and synapses in human neuropsychiatric disorders. Hum Pathol. 1975 Sep;6(5):571-82. doi: 10.1016/s0046-8177(75)80042-6. PMID: 170188.

Marin-Padilla M. Abnormal neuronal differentiation (functional maturation) in mental retardation. Birth Defects Orig Artic Ser. 1975;11(7):133-53. PMID: 764896.

Purpura DP. Normal and aberrant neuronal development in the cerebral cortex of human fetus and young infant. UCLA Forum Med Sci. 1975;(18):141-69. doi: 10.1016/b978-0-12-139050-1.50014-8. PMID: 128168.

Purpura DP. Dendritic spine "dysgenesis" and mental retardation. Science. 1974 Dec 20;186(4169):1126-8. doi: 10.1126/science.186.4169.1126. PMID: 4469701.

Search : decrease of drebrin

Xie MJ, Yagi H, Iguchi T, Yamazaki H, Hanamura K, Matsuzaki H, Shirao T, Sato M. Phldb2 is essential for regulating hippocampal dendritic spine morphology through drebrin in an adult-type isoform-specific manner. Neurosci Res. 2022 Dec;185:1-10. doi: 10.1016/j.neures.2022.09.010. Epub 2022 Sep 23. PMID: 36162735.