Related Experiment Video
Updated: May 27, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
G protein-coupled estrogen receptor deficiency exacerbates demyelination through microglial ferroptosis
Xiaojuan Mi1, Junjie Li1, Ziqi Feng1
1School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
Abstract:
Microglial activation is the initial pathological event that occurs in demyelination, a prevalent feature in various neurological diseases. G protein-coupled estrogen receptor 1 (GPER1), which is highly expressed in microglia, has been reported to reduce myelin damage. However, the precise molecular mechanisms involved remain unclear. In this study, the cuprizone (CPZ)-induced demyelination model was used to investigate the relationship between GPER1 and myelin sheath injury and its mechanism. The results demonstrated that GPER1 deficiency exacerbated cognitive impairment in mice. Along with more severe myelin damage as well as fewer oligodendrocytes. Moreover, GPER1 deficiency not only directly reduced the number of microglia in cuprizone mice but also caused iron ions overload in microglia of myelin debris induced in vitro. Transcriptomic, molecular biological, and morphological analyses revealed that microglial ferroptosis caused by GPER1 deficiency contributes to the reduction of microglia number. In summary, these findings revealed that GPER1 can regulate demyelination through ferroptosis of microglia.
Insights
G protein-coupled estrogen receptor 1 (GPER1) deficiency worsens demyelination and cognitive impairment by increasing microglial ferroptosis. This highlights GPER1
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial activation initiates demyelination in neurological diseases.
- G protein-coupled estrogen receptor 1 (GPER1) expressed in microglia may mitigate myelin damage.
- The exact molecular pathways linking GPER1 to myelin protection are not fully understood.
Purpose of the Study:
- To investigate the role of GPER1 in the cuprizone (CPZ)-induced demyelination model.
- To elucidate the molecular mechanisms by which GPER1 influences myelin sheath integrity and microglial function.
Main Methods:
- Utilized the cuprizone (CPZ)-induced demyelination mouse model.
- Conducted in vitro experiments to study microglia and myelin debris.
- Employed transcriptomic, molecular biological, and morphological analyses.
Main Results:
- GPER1 deficiency aggravated cognitive deficits, myelin damage, and oligodendrocyte loss in CPZ mice.
- GPER1 deficiency reduced microglial numbers and caused iron overload in microglia.
- Microglial ferroptosis, driven by GPER1 deficiency, was identified as the cause of reduced microglia.
Conclusions:
- GPER1 plays a crucial role in protecting against demyelination.
- GPER1 regulates demyelination by inhibiting microglial ferroptosis.
- Targeting GPER1 may offer a therapeutic strategy for demyelinating diseases.
More Related Videos
Related Concept Videos
01:21G-protein Coupled Receptors
01:12GPCR Desensitization
01:16Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...