Identification of metabolite biomarkers for L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease by metabolomic technology
Autor: | Lu Yao, Ge-Juan Zhang, Yi-Na Sun, Li Zhang, Yong Wang, Jian Liu, Cheng-Xue Du, Hui-Sheng Wang |
---|---|
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Dyskinesia Drug-Induced Parkinson's disease Apomorphine genetic structures Polyunsaturated Alkamides Metabolite Arachidonic Acids Striatum Motor Activity Pharmacology Glycerides Antiparkinson Agents Levodopa Rats Sprague-Dawley Pathogenesis 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Metabolomics Parkinsonian Disorders Animals Medicine Oxidopamine Cannabinoid Receptor Agonists business.industry medicine.disease Sphingolipid Endocannabinoid system Corpus Striatum eye diseases body regions Disease Models Animal 030104 developmental biology chemistry Dyskinesia Dopamine Agonists Metabolome sense organs medicine.symptom business Biomarkers 030217 neurology & neurosurgery Endocannabinoids |
Zdroj: | Behavioural Brain Research. 347:175-183 |
ISSN: | 0166-4328 |
Popis: | L-DOPA-induced dyskinesia (LID) is a frequent complication of chronic L-DOPA therapy in the clinical treatment of Parkinson's disease (PD). The pathogenesis of LID involves complex molecular mechanisms in the striatum. Metabolomics can shed light on striatal metabolic alterations in LID. In the present study, we compared metabolomics profiles of striatum tissue from Parkinsonian rats with or without dyskinetic symptoms after chronic L-DOPA administration. A liquid chromatography-mass spectrometry based global metabolomics method combined with multivariate statistical analyses were used to detect candidate metabolites associated with LID. 36 dysregulated metabolites in the striatum of LID rats, including anandamide, 2-arachidonoylglycerol, adenosine, glutamate and sphingosine1-phosphate were identified. Furthermore, IMPaLA metabolite set analysis software was used to identify differentially regulated metabolic pathways. The results showed that the metabolic pathways of "Retrograde endocannabinoid signaling", "Phospholipase D signaling pathway", "Glycerophospholipid metabolism" and "Sphingolipid signaling", etc. were dysregulated in LID rats compared to non-LID controls. Moreover, integrated pathway analysis based on results from the present metabolomics and our previous gene expression data in LID rats further demonstrates that aberrant "Retrograde endocannabinoid signaling" pathway might be involved in the development of LID. The present results provide a new profile for the understanding of the pathological mechanism of LID. |
Databáze: | OpenAIRE |
Externí odkaz: |