ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2015
Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Allopregnanolone Treatment Improves Plasma Metabolomic Profile Associated with GABA Metabolism in Fragile X-Associated Tremor/Ataxia Syndrome: a Pilot Study.Molecular neurobiology · 2019Trial
- Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.Translational psychiatry · 2024Article
- Untargeted Metabolomic Profiling Reveals Differentially Expressed Serum Metabolites and Pathways in Type 2 Diabetes Patients with and without Cognitive Decline: A Cross-Sectional Study.International journal of molecular sciences · 2024Article
- Association of Plasma Selenium and Its Untargeted Metabolomic Profiling with Cervical Cancer Prognosis.Biological trace element research · 2023Observational
- The Antipsychotic Risperidone Alters Dihydroceramide and Ceramide Composition and Plasma Membrane Function in Leukocytes In Vitro and In Vivo.International journal of molecular sciences · 2021Article
- Cerebrospinal fluid metabolomics identifies 19 brain-related phenotype associations.Communications biology · 2021Article
- Assessing the Causal Effects of Human Serum Metabolites on 5 Major Psychiatric Disorders.Schizophrenia bulletin · 2020Article
- Metabolomics in Psychiatric Disorders: What We Learn from Animal Models.Metabolites · 2020Review
- Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods.Advanced drug delivery reviews · 2020Review
- Untargeted Metabolomics Reveals Molecular Effects of Ketogenic Diet on Healthy and Tumor Xenograft Mouse Models.International journal of molecular sciences · 2019Article
- The Differences of Serum Metabolites Between Patients With Early-Stage Alzheimer's Disease and Mild Cognitive Impairment.Frontiers in neurology · 2019Article
- Association Study of the Complement Component C4 Gene in Tardive Dyskinesia.Frontiers in pharmacology · 2019Article
- Disrupted sphingolipid metabolism following acute clozapine and olanzapine administration.Journal of biomedical science · 2018Article
- Serum metabolite profile associates with the development of metabolic co-morbidities in first-episode psychosis.Translational psychiatry · 2016Article
- Omics-Based Biomarkers: Application of Metabolomics in Neuropsychiatric Disorders.The international journal of neuropsychopharmacology · 2015Review
- The Role of Metabolomics in Brain Metabolism Research.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.