Abstract
Converging evidence suggests that changes in plasma levels of amino acids are involved in Parkinson’s disease (PD), but their roles in nonmotor symptoms (NMS) of PD remain unclear. The aim of this study was to evaluate the correlations between plasma amino acids and NMS of PD. Plasma levels of aspartate (Asp), glutamate (Glu), glycine (Gly) and γ-aminobutyric acid (GABA) were measured in 92 PD patients and 60 healthy controls. Four NMS, including depression, pain, sleep disturbances and autonomic dysfunction were assessed in enrolled subjects using the Hamilton Depression Scale, the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to evaluate the correlations between plasma levels of amino acids and NMS. PD patients exhibited significantly higher scores of NMS scales and lower plasma levels of amino acids compared to healthy controls. Within the PD group, plasma levels of Asp and Glu were negatively associated with the severity of depression and sleep disturbances. Moreover, decreased plasma level of GABA was correlated with more severe symptoms of sleep disturbances. After controlling for gender, disease duration, severity of motor symptoms and anti-parkinsonian medications, Glu but not Asp remained significantly associated with depression, along with Asp, GABA but not Glu remained negatively associated with sleep disturbances. The altered plasma levels of amino acids may be implicated in the pathogenesis of NMS of PD.
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Alexander GM, Reichenberger E, Peterlin BL, Perreault MJ, Grothusen JR, Schwartzman RJ (2013) Plasma amino acids changes in complex regional pain syndrome. Pain Res Treat 2013:742407
Araki K, Takino T, Ida S, Kuriyama K (1986) Alteration of amino acids in cerebrospinal fluid from patients with Parkinson’s disease and spinocerebellar degeneration. Acta Neurol Scand 73:105–110
Bongiovanni R, Kirkbride B, Newbould E, Durkalski V, Jaskiw GE (2010) Relationships between large neutral amino acid levels in plasma, cerebrospinal fluid, brain microdialysate and brain tissue in the rat. Brain Res 1334:45–57
Brooks PL, Peever JH (2011) Impaired GABA and glycine transmission triggers cardinal features of rapid eye movement sleep behavior disorder in mice. J Neurosci 31:7111–7121
Buysse DJ, Reynolds CF, Monk TH, Hoch CC (1991) Quantification of subjective sleep quality in healthy elderly men and women using the Pittsburgh Sleep Quality Index (PSQI). Sleep 14(4):331–338
Chaudhuri KR, Schapira AH (2009) Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 8:464–474
Conditions NCCfC Parkinson’s disease: national clinical guideline for diagnosis and management in primary and secondary care (2006), Royal College of Physicians
Emir UE, Tuite PJ, Oz G (2012) Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS. PLoS One 7:e30918
Fahn S, Elton RL, Committee UD (1987) Unified Parkinson’s disease rating scale. Recent Dev Parkinson’s Dis 2:153–163
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Frye MA, Tsai GE, Huggins T, Coyle JT, Post RM (2007) Low cerebrospinal fluid glutamate and glycine in refractory affective disorder. Biol Psychiatry 61:162–166
Griffith HR, Okonkwo OC, O’Brien T, Hollander JA (2008) Reduced brain glutamate in patients with Parkinson’s disease. NMR Biomed 21:381–387
Hagenfeldt L, Bjerkenstedt L, Edman G, Sedvall G, Wiesel FA (1984) Amino acids in plasma and CSF and monoamine metabolites in CSF: interrelationship in healthy subjects. J Neurochem 42:833–837
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62
Huber DA, Schreihofer AM (2011) Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats. Am J Physiol Heart Circ Physiol 301:H230–H240
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184
Iwasaki Y, Ikeda K, Shiojima T, Kinoshita M (1992) Increased plasma concentrations of aspartate, glutamate and glycine in Parkinson’s disease. Neurosci Lett 145:175–177
Jimenez-Jimenez F et al (1998) Neurotransmitter amino acids in cerebrospinal fluid of patients with Alzheimer’s disease. J Neural Transm 105:269–277
Jiménez-Jiménez FJ et al (1996) Neurotransmitter amino acids in cerebrospinal fluid of patients with Parkinson’s disease. J Neurol Sci 141:39–44
Kim HJ et al (2009) Nonmotor symptoms in de novo Parkinson disease before and after dopaminergic treatment. J Neurol Sci 287:200–204
Li H, Zhang M, Chen L, Zhang J, Pei Z, Hu A, Wang Q (2010) Nonmotor symptoms are independently associated with impaired health-related quality of life in Chinese patients with Parkinson’s disease. Mov Disord 25:2740–2746
Melzack R (1987) The short-form McGill Pain Questionnaire. Pain 30:191–197
Mitani H, Shirayama Y, Yamada T, Maeda K, Ashby CR, Kawahara R (2006) Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog Neuropsychopharmacol Biol Psychiatry 30:1155–1158
Modrego PJ, Fayed N, Artal J, Olmos S (2011) Correlation of findings in advanced MRI techniques with global severity scales in patients with Parkinson disease. Acad Radiol 18:235–241
Molina JA et al (1997) Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson’s disease. J Neurol Sci 150:123–127
Murakami T, Yamane H, Tomonaga S, Furuse M (2009) Forced swimming and imipramine modify plasma and brain amino acid concentrations in mice. Eur J Pharmacol 602:73–77
Park A, Stacy M (2009) Non-motor symptoms in Parkinson’s disease. J Neurol 256(Suppl 3):293–298
Perschak H, Amsler U, Vischer A, Siegfried J, Cuenod M (1987) Ventricular cerebrospinal fluid concentrations of putative amino acid transmitters in Parkinson’s disease and other disorders. Hum Neurobiol 6:191–194
Sanacora G, Treccani G, Popoli M (2012) Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology 62:63–77
Santos-Garcia D, de la Fuente-Fernandez R (2013) Impact of non-motor symptoms on health-related and perceived quality of life in Parkinson’s disease. J Neurol Sci 332:136–140
Seppi K et al (2011) The movement disorder society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord 26(Suppl 3):S42–S80
Sun Z, Jia J, Gong X, Jia Y, Deng J, Wang X (2012) Inhibition of glutamate and acetylcholine release in behavioral improvement induced by electroacupuncture in parkinsonian rats. Neurosci Lett 520:32–37
Tohgi H, Abe T, Hashiguchi K, Takahashi S, Nozaki Y, Kikuchi T (1991) A significant reduction of putative transmitter amino acids in cerebrospinal fluid of patients with Parkinson’s disease and spinocerebellar degeneration. Neurosci Lett 126:155–158
Uhlhaas S, Lange H, Wappenschmidt J, Olek K (1986) Free and conjugated CSF and plasma GABA in Huntington’s chorea. Acta Neurol Scand 74:261–265
Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ (2004) Assessment of autonomic dysfunction in Parkinson’s disease: the SCOPA-AUT. Mov Disord 19:1306–1312
Watson CJ, Lydic R, Baghdoyan HA (2007) Sleep and GABA levels in the oral part of rat pontine reticular formation are decreased by local and systemic administration of morphine. Neuroscience 144:375–386
Wenzelburger R et al (2002) Force overflow and levodopa-induced dyskinesias in Parkinson’s disease. Brain 125:871–879
Yuan YS, Zhou XJ, Tong Q, Zhang L, Qi ZQ, Ge S, Zhang KZ (2013) Change in plasma levels of amino acid neurotransmitters and its correlation with clinical heterogeneity in early Parkinson’s disease patients. CNS Neurosci Ther 19:889–896
Acknowledgments
This work was supported by the University Natural Science Research Project in Jiangsu Province (No. 13KJB32009), the Natural science foundation of Jiangsu Province (No. BK20141494), the Opening Project of Jiangsu Key Laboratory of Neurodegeneration (No. SJ11KF01) and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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The authors declare that they have no conflict of interest.
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Q. Tong, Q. Xu and Q. Xia contributed equally to this work.
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Tong, Q., Xu, Q., Xia, Q. et al. Correlations between plasma levels of amino acids and nonmotor symptoms in Parkinson’s disease. J Neural Transm 122, 411–417 (2015). https://doi.org/10.1007/s00702-014-1280-5
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DOI: https://doi.org/10.1007/s00702-014-1280-5