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.
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.
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.
Aging, Cognitive function, Brain-derived estrogen, GPR30, Neuroprotection
Conditional Knockout model, Forebrain neuron-specific Cre driver, Aromatase gene deletion, Estrogen receptor signaling
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