Brain-derived Estrogen: A Critical Player in Maintaining Cognitive Health of Aged Female Rats, Possibly Involving GPR30

January 1, 2023
Neurobiol Aging
https://pubmed.ncbi.nlm.nih.gov/37257405

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/37257405

Research summary

This study investigates the role of brain-derived estrogen (BDE2) in cognitive function during aging in female rats. Researchers observed that estrogen synthesis is more active in the healthy aged brain, with increased expression of aromatase, the key enzyme for estrogen biosynthesis. Using a forebrain neuron-specific aromatase conditional Knockout (FBN-Aro-KO) rat model, they demonstrated that deletion of aromatase in forebrain neurons impaired hippocampal and cortical neurons and cognitive function in aged rats. Additionally, while nuclear estrogen receptors (ERα/β) showed differential expression changes, the membrane receptor GPR30 remained stable in the hippocampus during aging but was decreased in the FBN-Aro-KO rats, suggesting its sensitivity to local estrogen synthesis.

Key outcome of the study

Brain-derived estrogen is crucial for maintaining cognitive health in aged female rats, with its deficiency leading to neuronal impairment and cognitive decline. The membrane estrogen receptor GPR30 appears to be involved in mediating these effects, highlighting potential therapeutic targets for age-related cognitive disorders.

Mouse model

Forebrain neuron-specific aromatase conditional Knockout (FBN-Aro-KO) rat model, generated by crossing rats harboring floxed aromatase alleles with rats expressing Cre recombinase under the control of a forebrain neuron-specific promoter, leading to targeted deletion of aromatase in forebrain neurons.

TARGET:
CYP19A1
Aromatase

Keywords

Aging, Cognitive function, Brain-derived estrogen, GPR30, Neuroprotection

Technical specifications

Conditional Knockout model, Forebrain neuron-specific Cre driver, Aromatase gene deletion, Estrogen receptor signaling

Related products

Catalogue product

No items found.

Customized product

Tissue-specific KO rats

Use  tissue- or cell-specific conditional Knockout rat models to bypass embryonic lethality,  compensatory mechanisms, complex phenotypes, etc.