Dataset Information

Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats.

ABSTRACT:

Background

Late-onset depression (LOD) is defined as primary depression that first manifests after the age of 65. Luteolin (LUT) is a natural flavonoid that has shown promising antidepressant effects and improvement in neurological function in previous studies.

Aims

In this study, we utilized UPLC-MS/MS non-targeted metabolomics techniques, along with molecular docking technology and experimental validation, to explore the mechanism of LUT in treating LOD from a metabolomics perspective.

Results

The behavioral results of our study demonstrate that LUT significantly ameliorated anxiety and depression-like behaviors while enhancing cognitive function in LOD rats. Metabolomic analysis revealed that the effects of LUT on LOD rats were primarily mediated through the glycerophospholipid metabolic pathway in the hippocampus and prefrontal cortex. The levels of key lipid metabolites, phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), in the glycerophospholipid metabolic pathway were significantly altered by LUT treatment, with PC and PE showing significant correlations with behavioral indices. Molecular docking analysis indicated that LUT had strong binding activity with phosphatidylserine synthase 1 (PTDSS1), phosphatidylserine synthase 2 (PTDSS2), and phosphatidylserine decarboxylase (PISD), which are involved in the transformation and synthesis of PC, PE, and PS. Lastly, our study explored the reasons for the opposing trends of PC, PE, and PS in the hippocampus and prefrontal cortex from the perspective of autophagy, which may be attributable to the bidirectional regulation of autophagy in distinct brain regions.

Conclusions

Our results revealed significant alterations in the glycerophospholipid metabolism pathways in both the hippocampus and prefrontal cortex of LOD rats. Moreover, LUT appears to regulate autophagy disorders by specifically modulating glycerophospholipid metabolism in different brain regions of LOD rats, consequently alleviating depression-like behavior in these animals.

SUBMITTER: Wu X

PROVIDER: S-EPMC10916417 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats.

Wu Xiaofeng X Xu Hanfang H Zeng Ningxi N Li Huizhen H Yao Gaolei G Liu Kaige K Yan Can C Wu Lili L

CNS neuroscience & therapeutics 20230916 3

<h4>Background</h4>Late-onset depression (LOD) is defined as primary depression that first manifests after the age of 65. Luteolin (LUT) is a natural flavonoid that has shown promising antidepressant effects and improvement in neurological function in previous studies.<h4>Aims</h4>In this study, we utilized UPLC-MS/MS non-targeted metabolomics techniques, along with molecular docking technology and experimental validation, to explore the mechanism of LUT in treating LOD from a metabolomics persp ...[more]

PMID: 37715585

Similar Datasets

Project description:BackgroundThe comparability of gene expression between blood and brain tissues is a central issue in neuropsychiatric research where the analysis of molecular mechanisms in the brain is of high importance for the understanding of the diseases and the discovery of biomarkers. However, the accessibility of brain tissue is limited. Therefore, knowledge about how easily accessible peripheral tissue, e. g. blood, is comparable to and reflects gene expression of brain regions will help to advance neuropsychiatric research.DescriptionGene expression in the blood, hippocampus (HC) and prefrontal cortex (PFC) of genetically identical rats was compared using a genome-wide Affymetrix gene expression microarray covering 29,215 expressed genes. A total of 56.8% of 15,717 expressed genes were co-expressed in blood and at least one brain tissue, while 55.3% of all genes were co-expressed in all three tissues simultaneously. The overlapping genes included a set of genes of relevance to neuropsychiatric diseases, in particular bipolar disorder, schizophrenia and alcohol addiction. These genes included CLOCK, COMT, FAAH, NPY, NR3C1, NRGN, PBRM1, TCF4, and SYNE.ConclusionsThis study provides baseline data on absolute gene expression and differences between gene expression in the blood, HC and PFC brain tissue of genetically identical rats. The present data represents a valuable resource for future studies as it might be used for first information on gene expression levels of genes of interest in blood and brain under baseline conditions. Limitations of our study comprise possible contamination of brain tissue with blood and the non-detection of genes with very low expression levels. Genes that are more highly expressed in the brain than in the blood are of particular interest since changes in their expression, e.g. due to disease status, or treatment, are likely to be detected in an experiment. In contrast, genes with higher expression in the blood than in the brain are less informative since their higher baseline levels could superimpose variation in brain.

Project description:IntroductionGlyphosate-based herbicides (GBHs) have been shown to have significant neurotoxic effects, affecting both the structure and function of the brain, and potentially contributing to the development of neurodegenerative disorders. Despite the known importance of glycosylation in disease progression, the glycome profile of systems exposed to GBH has not been thoroughly investigated.MethodsIn this study, we conducted a comprehensive glycomic profiling using LC-MS/MS, on the hippocampus and prefrontal cortex (PFC) of juvenile rats exposed to GBH orally, aiming to identify glyco-signature aberrations after herbicide exposure.ResultsWe observed changes in the glycome profile, particularly in fucosylated, high mannose, and sialofucosylated N-glycans, which may be triggered by GBH exposure. Moreover, we found major significant differences in the N-glycan profiles between the GBH-exposed group and the control group when analyzing each gender independently, in contrast to the analysis that included both genders. Notably, gender differences in the behavioral test of object recognition showed a decreased performance in female animals exposed to GBH compared to controls (p < 0.05), while normal behavior was recorded in GBH-exposed male rats (p > 0.05).ConclusionThese findings suggest that glycans may play a role in the neurotoxic effect caused by GBH. The result suggests that gender variation may influence the response to GBH exposure, with potential implications for disease progression and specifically the neurotoxic effects of GBHs. Understanding these gender-specific responses could enhance knowledge of the mechanisms underlying GBH-induced toxicity and its impact on brain health. Overall, our study represents the first detailed analysis of N-glycome profiles in the hippocampus and PFC of rats chronically exposed to GBH. The observed alterations in the expression of N-glycan structures suggest a potential neurotoxic effect associated with chronic GBH exposure, highlighting the importance of further research in this area.

Project description:IntroductionPost-stroke depression (PSD) is the most common complication following a stroke, significantly hindering recovery and rehabilitation in affected patients. Despite its prevalence, the pathogenesis of PSD remains poorly understood. Electroacupuncture (EA) has shown antidepressant effects, yet its neuroprotective properties are not well defined. Ferroptosis, a recently identified form of cell death, is implicated in the pathological processes of stroke and is associated with the development of depression-like behaviors. So we aimed to investigate whether PSD induces ferroptosis, identify potential therapeutic targets within these pathways, and elucidate the underlying mechanisms in this study.MethodsMale Sprague-Dawley rats were subjected to middle carotid artery occlusion and chronic unpredictable mild stress to model PSD. To explore the role of ferroptosis in the effects of EA, the ferroptosis inducer erastin was administered into the rats' lateral ventricles, followed by 14 days of EA treatment, with sessions lasting 30 minutes per day. The Zea-Longa score was used to assess neurological deficits, while the sucrose preference test, elevated plus maze test, and open-field test were employed to evaluate depression-like behaviors in the rats. Hematoxylin-eosin, Nissl, and Perl's staining were used to observe the morphological changes and iron deposition in the prefrontal neurons. Transmission electron microscopy provided detailed observations of mitochondrial morphological changes in neurons. We utilized activity assay kits, enzyme-linked immunosorbent assay (ELISA), and Western blotting to explore potential molecular mechanisms underlying the effects of EA.ResultsEA can reduce neurological deficits and enhance the spontaneous activity and exploration behavior of rats. In addition, EA could inhibit prefrontal cortex neuronal ferroptosis by reducing iron deposition, decreasing lipid peroxidation, and enhancing antioxidation.DiscussionEA improved depression-like behaviors, mitigated mitochondrial damage, and inhibited ferroptosis in prefrontal cortex neurons. Notably, the administration of erastin further enhanced these effects. In conclusion, EA appears to improve PSD by inhibiting ferroptosis in the prefrontal cortex.

Project description:BackgroundGegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine (TCM) formula primarily utilized for treating gut disorders. GQD showed therapeutic effects on several diseases in clinical and animal studies by targeting gut microbes. Our recent studies also found that GQD efficiently alleviated anxiety in methamphetamine-withdrawn mice via regulating gut microbiome and metabolism. Given that various studies have indicated the link between the gut microbiome and the development of depression, here we endeavor to explore whether GQD can manage depression disorders by targeting the gut microbiome.Methods and materialsThe depression-like model was induced in rats through chronic unpredictable mild stress (CUMS) and the depression levels were determined using the sucrose preference test (SPT). To address the depression-like behavior in rats, oral administration of GQD was employed. The colon microbiome and metabolite patterns were determined by 16s rRNA sequencing and untargeted metabolomics, respectively.ResultsWe found 6 weeks of CUMS can induce depression-like behavior in rats and 4 weeks of GQD treatment can significantly alleviate the depression-like behavior. GQD treatment can also ameliorate the histological lesions in the colon of CUMS rats. Then, CUMS increased the abundance of gut microbes, while GQD treatment can restore it to a lower level. We further discovered that the abundances of 19 bacteria at the genus level were changed with CUMS treatment, among which the abundances of Ruminococcus, Lachnoclostridium, Pygmaiobacter, Bacteroides, Pseudomonas, and Pseudomonas Family_XIII_AD3011_group were stored by GQD treatment. Besides, we identified the levels of 36 colon metabolites were changed with CUMS treatment, among which the levels of Fasciculic acid B, Spermine, Fludrocortisone acetate, alpha-Ketoglutaric acid, 2-Oxoglutaric acid, N'-(benzoyloxy)-2-(2,2-dichlorocyclopropyl) ethanimidamide, N6-Succinyl Adenosine Oleanolic acid, KQH, Ergosta-5,7,9(11),22-Tetraen-3-beta-Ol, Gentisic acid, 4-Hydroxyretinoic Acid, FAHFA (3:0/16:0), Leucine-enkephalin and N-lactoyl-phenylalanine can be restored by GQD treatment.ConclusionOur findings provide evidence supporting the therapeutic efficacy of GQD in alleviating depression-like behavior in CUMS rats, potentially being targeted on colon bacteria (especially the abundance of Ruminococcus and Bacteroides) and metabolites (especially the level of Oleanolic acid).

Dataset Information

Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats.

Background

Aims

Results

Conclusions

Publications

Luteolin alleviates depression-like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets