Metabolomic abnormalities of purine and lipids implicated olfactory bulb dysfunction of CUMS depressive rats

He, Yong; Wang, Yue; Wu, Zhonghao; Lan, Tianlan; Tian, Yu; Chen, Xi; Li, Yan; Dang, Ruozhi; Bai, Mengge; Cheng, Ke; Xie, Peng

doi:10.1007/s11011-020-00557-8

Cited by 18 publications

(12 citation statements)

References 48 publications

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“…Additionally, acetyl coenzyme A regulating depression through fatty acid metabolism also provided theoretical foundation for our finding. Interestingly, A large number of research demonstrated that purine metabolism is dysregulated in patients with major depressive disorder (Ali-Sisto et al, 2016;He et al, 2020), consistent with our findings, P164-PWY (purine nucleobases degradation I (anaerobic))] was different in three groups. These data provide mechanistic insights into how prostate microbiota controls brain function.…”

Section: Discussionsupporting

confidence: 90%

Abnormal prostate microbiota composition is associated with experimental autoimmune prostatitis complicated with depression in rats

Liu

Xu²,

Wang³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundMicrobiota play essential roles in the pathogenesis of prostatitis and depression. However, the changes in prostate microbiota have not yet been explored in rats with prostatitis/depression. This study aimed to investigate the changes of prostate microbiota in rats with prostatitis/depression.MethodsRats with experimental autoimmune prostatitis (EAP) complicated with depression were constructed through injection of rat prostate antigen with immunoadjuvants followed by application of chronic unpredictable mild stress (CUMS). The rats were subjected to inflammatory factor detection and behavioral testing to confirm the establishment of the model. Subsequently, the prostate microbiota was assayed in the rats and compared by 16S rRNA gene sequencing.ResultsA rat model of EAP complicated with depression was established and confirmed by increases in IL-1β, IL-6, and TNF-α as well as the occurrence of depressive‐like behaviors. EAP/CUMS significantly altered the richness, evenness, and composition of prostate microbiota. Forty-six taxonomic biomarkers for prostate microbiota were enriched in rats with EAP/depression and exhibited statistically significant and biologically consistent differences. Metabolomics profiling revealed that EAP/depression was associated with reductive acetyl coenzyme A pathway, L-lysine fermentation to acetate and butanoate, protein N-glycosylation and purine nucleobases degradation I, which is regulated by DCE29, Nocardioes, Helicobacter and Dorea.ConclusionFindings from the study demonstrate the existence of abnormal prostate microbiota in EAP complicated with depression and may be helpful in the treatment of comorbid diseases of prostatitis and depression.

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Section: Discussionsupporting

confidence: 90%

Abnormal prostate microbiota composition is associated with experimental autoimmune prostatitis complicated with depression in rats

Liu

Xu²,

Wang³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…In the hippocampus of rats subjected to physical or psychological stressors, lactic acid was one of nine metabolites altered in all stress contexts, revealing the universal impact of chronic stress on glycolysis and mitochondrial function of this brain region 54 . And in rats subjected to chronic unpredictable stress, disturbances in purine metabolism were identified in the olfactory bulb 55 , hinting that purine metabolism may be sensitive to stress in brain regions that were not investigated in the present study.…”

Section: Discussionmentioning

confidence: 73%

Chronic stress and antidepressant treatment alter purine metabolism and beta oxidation within mouse brain and serum

Hamilton

Chen²,

Tolstikov³

et al. 2020

Sci Rep

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Major depressive disorder (MDD) is a complex condition with unclear pathophysiology. Molecular disruptions within limbic brain regions and the periphery contribute to depression symptomatology and a more complete understanding the diversity of molecular changes that occur in these tissues may guide the development of more efficacious antidepressant treatments. Here, we utilized a mouse chronic social stress model for the study of MDD and performed metabolomic, lipidomic, and proteomic profiling on serum plus several brain regions (ventral hippocampus, nucleus accumbens, and medial prefrontal cortex) of susceptible, resilient, and unstressed control mice. To identify how commonly used tricyclic antidepressants impact the molecular composition in these tissues, we treated stress-exposed mice with imipramine and repeated our multi-OMIC analyses. Proteomic analysis identified three serum proteins reduced in susceptible animals; lipidomic analysis detected differences in lipid species between resilient and susceptible animals in serum and brain; and metabolomic analysis revealed dysfunction of purine metabolism, beta oxidation, and antioxidants, which were differentially associated with stress susceptibility vs resilience by brain region. Antidepressant treatment ameliorated stress-induced behavioral abnormalities and affected key metabolites within outlined networks, most dramatically in the ventral hippocampus. This work presents a resource for chronic social stress-induced, tissue-specific changes in proteins, lipids, and metabolites and illuminates how molecular dysfunctions contribute to individual differences in stress sensitivity.

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“…The effect of the tricyclic antidepressant imipramine on purine metabolism has also been shown on mice in a model of depression [24]. It was demonstrated that purines play an important role in neuromodulation and neurotransmission, cellular-growth-related signaling, and energy metabolism [62]. There is a correlation found between purine metabolite concentration levels in spinal fluid and the concentration levels of monoamine metabolites such as homovanillic acid and 5-hydroxyindoleacetic acid, which proves a parallel metabolism of purines and monoamines in brain tissue [63].…”

Section: Discussionmentioning

confidence: 99%

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

Abramova

Zorkina

Syunyakov

et al. 2021

IJMS

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Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

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Metabolomic abnormalities of purine and lipids implicated olfactory bulb dysfunction of CUMS depressive rats

Cited by 18 publications

References 48 publications

Abnormal prostate microbiota composition is associated with experimental autoimmune prostatitis complicated with depression in rats

Abnormal prostate microbiota composition is associated with experimental autoimmune prostatitis complicated with depression in rats

Chronic stress and antidepressant treatment alter purine metabolism and beta oxidation within mouse brain and serum

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

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