Untargeted metabolomics revealed that quercetin improved metabolism
dysregulation in the prefrontal cortex of perimenopausal depression rat
model
Abstract
Perimenopausal depression is a subtype of depression and its
pathogenesis is still unclear, which affects its prevention and
treatment to a certain extent. Prefrontal cortex (PFC) is an advanced
center for cognitive and emotional integration, which is intimately
connected to the development of perimenopausal depression. Using an
untargeted metabolomic analysis, the study attempts to explore whether
quercetin can have a protective effect on perimenopausal depression.
Female Wistar rats were randomly divided into 4 experimental groups
(n=12): the sham group, the model group, the model+17β-estradiol (E
2) intervention group (0.27 mg/kg.bw), the
model+quercetin intervention group (50 mg/kg.bw). Subsequently,
perimenopausal depression rat model was established using ovariectomy
(OVX) combined with chronic unpredictable mild stress (CUMS). After the
experiment, tissues from PFC were collected for subsequent metabolomic
analyses as well as the detection of phospholipase A 2 (PLA2),
arachidonate 5-lipoxygenase (ALOX5) and malondialdehyde (MDA). A total
of 13 differential metabolites were identified in the model group, and a
pathway enrichment analysis indicated that the metabolism disorders of
PFC were mainly related to lipid metabolism, amino acid metabolism, and
carnitine synthesis. Notably, this study further discovered that lipid
metabolism disorders might cause ferroptosis in PFC of rat model with
perimenopausal depression. These changes in differential metabolites
were normalized after an intervention with quercetin and E
2, suggesting that quercetin could regulate the
metabolic disorders of PFC in perimenopausal depression rat model via
exerting the estrogen-like and neuroprotective effect. Quercetin may be
a potential adjuvant for perimenopausal depression.