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Key Event: 1329

Key Event Title

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

Brain-derived neurotrophic factor (BDNF) gene expression, reduced

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

BDNF gene expression, reduced

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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
Molecular

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

Organ term

Organ term
brain

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
gene expression	brain-derived neurotrophic factor	decreased

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
Network of SSRIs	KeyEvent	Lyle Burgoon (send email)	Open for adoption
Mental stress to depression	KeyEvent	Lyle Burgoon (send email)	Open for adoption
Mental stress to agitation	KeyEvent	Lyle Burgoon (send email)	Open for adoption
Serotonin transporter activation to agitation	KeyEvent	Lyle Burgoon (send email)	Open for adoption
Serotonin transporter activation to depression	KeyEvent	Lyle Burgoon (send email)	Open for adoption

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
Mammalia	Mammalia	High	NCBI
rodentia	rodentia	High	NCBI
Homo sapiens	Homo sapiens	Moderate	NCBI

Life Stages

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

Life stage	Evidence
Adult	High
Adults	High
During brain development	Moderate

Sex Applicability

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

Term	Evidence
Unspecific	Moderate

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

Brain-derived neurotrophic factor (BDNF) is a neurotrophin gene expressed prominently in the central nervous system. This key event refers specifically to a decrease in BDNF/Bdnf mRNA transcript abundance relative to an appropriate control in a defined biological compartment, typically neural tissue or neural cells.

Foundational studies established that BDNF mRNA is expressed predominantly in the central nervous system (Leibrock et al., 1989). In adult mouse brain, BDNF mRNA is broadly distributed across regions, with highest levels in hippocampus and substantial expression in cerebral cortex; in situ hybridization localized BDNF mRNA to hippocampal pyramidal and granule neurons (Hofer et al., 1990). These findings support the biological relevance of this key event in brain regions important for neuronal plasticity and function.

BDNF transcription is dynamically regulated by neuronal activity. In the mammalian brain, membrane depolarization and calcium influx through voltage-gated calcium channels and NMDA receptors promote transcriptional activation of BDNF, and both rodent and human BDNF genes use multiple promoters that contribute to context-dependent regulation (Park & Poo, 2013).

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

RT-qPCR for targeted quantification of BDNF/Bdnf transcript abundance in neural tissue or cultured neural cells.
RNA sequencing or other transcriptomic platforms for broader assessment of BDNF transcript levels.
Northern blot analysis, used in foundational studies to detect and compare BDNF mRNA expression across tissues and brain regions (Leibrock et al., 1989; Hofer et al., 1990).
In situ hybridization for anatomical localization of BDNF mRNA within specific brain regions or cell populations (Hofer et al., 1990).

Domain of Applicability

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

Taxonomic Applicability

Strongest support: Mammals, especially rodents and humans. Direct evidence for this key event comes primarily from mammalian studies of BDNF mRNA expression and regulation (Leibrock et al., 1989; Hofer et al., 1990; Park & Poo, 2013).

Life Stage Applicability

Supported: During brain development and adulthood; plausibly aging. BDNF is involved in neural development, neuronal differentiation, and synaptic plasticity, and BDNF mRNA is clearly expressed in adult brain (Binder & Scharfman, 2004; Hofer et al., 1990; Park & Poo, 2013). Applicability to aging is biologically plausible, although direct support in the cited primary literature is more limited.

Sex Applicability

Unspecific. BDNF gene expression is a general feature of mammalian brain biology.

References

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

Barde, Y.-A., Edgar, D., & Thoenen, H. (1982). Purification of a new neurotrophic factor from mammalian brain. The EMBO Journal, 1(5), 549–553.

Binder, D. K., & Scharfman, H. E. (2004). Brain-derived neurotrophic factor. Growth Factors, 22(3), 123–131.

Hofer, M., Pagliusi, S. R., Hohn, A., Leibrock, J., & Barde, Y.-A. (1990). Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. The EMBO Journal, 9(8), 2459–2464.

Leibrock, J., Lottspeich, F., Hohn, A., Hofer, M., Hengerer, B., Masiakowski, P., Thoenen, H., & Barde, Y.-A. (1989). Molecular cloning and expression of brain-derived neurotrophic factor. Nature, 341, 149–152.

Park, H., & Poo, M.-m. (2013). Neurotrophin regulation of neural circuit development and function. Nature Reviews Neuroscience, 14(1), 7–23.