Restricted accessResearch articleFirst published online 2020-07-13
Melatonin and dopamine serum level associations with motor,cognitive,and sleep dysfunctions in patients with Parkinson’s disease: A cross-sectional research study
Parkinson’s disease (PD) is a multisystem-progressive neurodegenerative disease characterized by dopaminergic neurons, however, the role of the non-dopaminergic system (such as melatonin hormone) in the pathogenesis of PD is now emerging.
OBJECTIVE:
To identify any potential correlation between the dopamine and melatonin serum levels, and motor, cognitive, and sleep dysfunctions in patients with PD.
METHOD:
Cross-sectional piloting study conducted with a sample of 34 patients with PD (aged 50–72 yrs old). Correlation tests performed to identify any potential correlations between the biomarkers’ serum levels and motor, cognitive, and sleep dysfunctional levels in “on-medication” status.
RESULTS:
Spearman’s test showed significant correlations between the melatonin serum level and sleep dysfunctions including overall sleep quality (P = 0.010) and subjective sleep quality sub-score (P = 0.001). On the other hand, spearman’s test showed significant correlations between the dopamine serum level and motor dysfunctions including Berg Balance Scale (P = 0.026), 10-Meter Walk Test (P = 0.016), and Fear of Falling Index (P = 0.007), as well as comparisons between the dopamine serum level and cognitive dysfunction (P = 0.048).
CONCLUSIONS:
Melatonin serum level would serve as a potential biomarker in understanding the PD pathogenesis, and the melatonin serum level should be considered in future studies related to PD besides the dopamine serum level.
Absi,E., Ayala,A., Machado,A., Parrado,J. (2000). Protective effect of melatonin against the 1-methyl-4phenylpyridinium-induced inhibition of complex I of the mitochondrial respiratory chain. Journal of pineal research, 29(1), 40–47.
2.
Alghamdi,B. (2018). The neuroprotective role of melatonin in neurological disorders. Journal of neuroscience research, 96(7), 1136–1149.
3.
Backhaus,J., Junghanns,K., Broocks,A., Riemann,D., Hohagen,F. (2002). Test–retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. Journal of psychosomatic research, 53(3), 737–740.
4.
Bassani,T. B., Gradowski,R. W., Zaminelli,T., Barbiero,J. K., Santiago,R. M., Boschen,S. L., da Cunha,C., Lima,M. M., Andreatini,R., Vital,M. A. (2014). Neuroprotective and antidepressant-like effects of melatonin in a rotenone-induced Parkinson’s disease model in rats. Brain Research, 1593, 95–105.
5.
Bloem,B. R., Marinus,J., Almeida,Q., Dibble,L., Nieuwboer,A., Post,B., Ruzicka,E., Goetz,C., Stebbins,G., Martinez-Martin,P. (2016). M easurement instruments to assess posture, gait, and balance in P arkinson’s disease: Critique and recommendations. Movement Disorders, 31(9), 1342–1355.
6.
Boutrel,B., Koob,G. F. (2004). What keeps us awake: the neuropharmacology of stimulants and wakefulness promoting medications. Sleep, 27(6), 1181–1194.
7.
Cardinali,D. P., Vigo,D. E., Olivar,N., Vidal,M. F., Furio,A. M., Brusco,L. I. (2012). Therapeutic application of melatonin in mild cognitive impairment. American Journal of Neurodegenerative Disease, 1(3), 280.
8.
Cools,R., Stefanova,E., Barker,R. A., Robbins,T. W., Owen,A. M. (2002). Dopaminergic modulation of high-level cognition in Parkinson’s disease: the role of the prefrontal cortex revealed by PET. Brain, 125(3), 584–594.
9.
Dabbeni-Sala,F., Disanto,S., Franceschini,D., Skaper,S. D., Giusti,P. (2001). Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity. The FASEB Journal, 15(1), 164–170.
10.
Datieva,V., Rosinskaia,A., Levin,O. (2013). The use of melatonin in the treatment of chronic fatigue syndrome and circadian rhythm disorders in Parkinson’s disease. Zhurnal nevrologii i psikhiatrii imeni SS Korsakova, 113(7 Pt 2), 77–81.
11.
Delenclos,M., Jones,D. R., McLean,P. J., Uitti,R. J. (2016). Biomarkers in Parkinson’s disease: Advances and strategies. Parkinsonism & Related Disorders, 22, S106–S110.
12.
Dowling,G. A., Mastick,J., Colling,E., Carter,J. H., Singer,C. M., Aminoff,M. J. (2005). Melatonin for sleep disturbances in Parkinson’s disease. Sleep Medicine, 6(5), 459–466.
13.
El-Ghundi,M., O’Dowd,B. F., George,S. R. (2007). Insights into the role of dopamine receptor systems in learning and memory. Reviews in the Neurosciences, 18(1), 37–66.
14.
Gutierrez-Valdez,A. L., Anaya-Martínez,V., Ordoñez-Librado,J. L., García-Ruiz,R., Torres-Esquivel,C., Moreno-Rivera,M., Sánchez-Betancourt,J., Montiel-Flores,E., Avila-Costa,M. R. (2012). Effect of chronic L-dopa or melatonin treatments after dopamine deafferentation in rats: dyskinesia, motor performance, and cytological analysis. ISRN Neurology, 2012.
15.
Hardeland,R., Poeggeler,B., Srinivasan,V., Trakht,I., Pandi-Perumal,S. R., Cardinali,D. P. (2008). Melatonergic drugs in clinical practice. Arzneimittelforschung, 58(01), 1–10.
16.
Hoops,S., Nazem,S., Siderowf,A., Duda,J., Xie,S., Stern,M., Weintraub,D. (2009). Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology, 73(21), 1738–1745.
17.
Jankovic,J. (2008). Parkinson’s disease: clinical features and diagnosis. Journal of Neurology, Neurosurgery & Psychiatry, 79(4), 368–376.
18.
Jenner,P. (1998). Oxidative mechanisms in nigral cell death in Parkinson’s disease. Movement Disorders: Official Journal of the Movement Disorder Society, 13, 24–34.
19.
Jenner,P. (2003). Oxidative stress in Parkinson’s disease. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 53(S3), S26–S38.
20.
Khaldy,H., Escames,G., Leon,J., Vives,F., Luna,J., Acuña-Castroviejo,D. (2000). Comparative effects of melatonin, l-deprenyl, Trolox and ascorbate in the suppression of hydroxyl radical formation during dopamine autoxidation in vitro. Journal of Pineal Research, 29(2), 100–107.
21.
Kunz,D., Bes,F. (1999). Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Movement Disorders: official Journal of the Movement Disorder Society, 14(3), 507–511.
22.
Leonard,A. (2016). The Relationship between Circadian Dysfunction and Cognitive Impairment in Individuals with Parkinson’s Disease. Undergraduate Review, 12(1), 80–89.
23.
Lin,L., Du,Y., Yuan,S., Shen,J., Lin,X., Zheng,Z. (2014). Serum melatonin is an alternative index of Parkinson’s disease severity. Brain Research, 1547, 43–48.
24.
Lindholm,B., Nilsson,M. H., Hansson,O., Hagell,P. (2018). The clinical significance of 10-m walk test standardizations in Parkinson’s disease. Journal of Neurology, 265(8), 1829–1835.
25.
Mack,J. M., Schamne,M. G., Sampaio,T. B., Pértile,R. A. N., Fernandes,P. A. C. M., Markus,R. P., Prediger,R. D. (2016). Melatoninergic system in Parkinson’s disease: from neuroprotection to the management of motor and nonmotor symptoms. Oxidative Medicine and Cellular Longevity, 2016.
26.
Maiti,P., Manna,J., Dunbar,G. L. (2017). Current understanding of the molecular mechanisms in Parkinson’s disease: targets for potential treatments. Translational Neurodegeneration, 6(1), 28.
27.
Mattay,V. S., Tessitore,A., Callicott,J. H., Bertolino,A., Goldberg,T. E., Chase,T. N., Hyde,T. M., Weinberger,D. R. (2002). Dopaminergic modulation of cortical function in patients with Parkinson’s disease. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 51(2), 156–164.
28.
Medeiros,C. A. M., De Bruin,P. F. C., Lopes,L. A., Magalhães,M. C., de Lourdes Seabra,M., de Bruin,V. M. S. (2007). Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson’s disease. Journal of Neurology, 254(4), 459–464.
29.
Mehdizadeh,M., Martinez-Martin,P., Habibi,S.-A., Fereshtehnejad,S.-M., Abasi,A., Niazi Khatoon,J., Saneii,S. H., Taghizadeh,G. (2019). Reliability and Validity of Fall Efficacy Scale-International in People with Parkinson’s Disease during On-and Off-Drug Phases. Parkinson’s Disease, 2019.
30.
Nieoullon,A. (2002). Dopamine and the regulation of cognition and attention. Progress in Neurobiology, 67(1), 53–83.
31.
Nishi,A., Kuroiwa,M., Shuto,T. (2011). Mechanisms for the modulation of dopamine D receptor signaling in striatal neurons. Frontiers in Neuroanatomy, 5, 43.
32.
Park,S. B., Kwon,K.-Y., Lee,J.-Y., Im,K., Sunwoo,J.-S., Lee,K. B., Roh,H., Ahn,M.-Y., Park,S., Kim,S.-J. (2019). Lack of association between dopamine transporter loss and non-motor symptoms in patients with Parkinson’s disease: a detailed PET analysis of 12 striatal subregions. Neurological Sciences, 40(2), 311–317.
33.
Paus,S., Schmitz-Hübsch,T., Wüllner,U., Vogel,A., Klockgether,T., Abele,M. (2007). Bright light therapy in Parkinson’s disease: a pilot study. Movement disorders: official journal of the Movement Disorder Society, 22(10), 1495–1498.
34.
Pevet,P., Bothorel,B., Slotten,H., Saboureau,M. (2002). The chronobiotic properties of melatonin. Cell and Tissue Research, 309(1), 183–191.
35.
Qu,W.-M., Xu,X.-H., Yan,M.-M., Wang,Y.-Q., Urade,Y., Huang,Z.-L. (2010). Essential role of dopamine D2 receptor in the maintenance of wakefulness, but not in homeostatic regulation of sleep, in mice. Journal of Neuroscience, 30(12), 4382–4389.
36.
Qutubuddin,A. A., Pegg,P. O., Cifu,D. X., Brown,R., McNamee,S., Carne,W. (2005). Validating the Berg Balance Scale for patients with Parkinson’s disease: a key to rehabilitation evaluation. Archives of Physical Medicine and Rehabilitation, 86(4), 789–792.
37.
Reiter,R. J., Tan,D.-x., Mayo,J. C., Sainz,R. M., Leon,J., Czarnocki,Z. (2003). Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta Biochimica Polonica-English Edition, 50(4), 1129–1146.
38.
Romenets,S. R., Creti,L., Fichten,C., Bailes,S., Libman,E., Pelletier,A., Postuma,R. (2013). Doxepin and cognitive behavioural therapy for insomnia in patients with Parkinson’s disease–a randomized study. Parkinsonism & Related Disorders, 19(7), 670–675.
39.
Rutten,S., Vriend,C., van den Heuvel,O. A., Smit,J. H., Berendse,H. W., van der Werf,Y. D. (2012). Bright light therapy in Parkinson’s disease: an overview of the background and evidence. Parkinson’s Disease, 2012.
40.
Serfaty,M., Kennell-Webb,S., Warner,J., Blizard,R., Raven,P. (2002). Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia. International Journal of Geriatric Psychiatry, 17(12), 1120–1127.
41.
Smarr,B. L., Jennings,K. J., Driscoll,J. R., Kriegsfeld,L. J. (2014). A time to remember: The role of circadian clocks in learning and memory. Behavioral Neuroscience, 128(3), 283.
42.
Vaught,S. L. (2001). Gait, balance, and fall prevention. Ochsner Journal, 3(2), 94–97.
43.
Videnovic,A., Noble,C., Reid,K. J., Peng,J., Turek,F. W., Marconi,A., Rademaker,A. W., Simuni,T., Zadikoff,C., Zee,P. C. (2014). Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease. JAMA Neurology, 71(4), 463–469.
44.
Willis,G. L., Armstrong,S. M. (1999). A therapeutic role for melatonin antagonism in experimental models of Parkinson’s disease. Physiology & Behavior, 66(5), 785–795.
45.
Willis,G. L., Moore,C., Armstrong,S. M. (2012). A historical justification for and retrospective analysis of the systematic application of light therapy in Parkinson’s disease. Reviews in the Neurosciences, 23(2), 199–226.
46.
Willis,G. L., Turner,E. J. D. (2007). Primary and secondary features of Parkinson’s disease improve with strategic exposure to bright light: a case series study. Chronobiology International, 24(3), 521–537.
47.
Wu,Y. H., Swaab,D. F. (2005). The human pineal gland and melatonin in aging and Alzheimer’s disease. Journal of Pineal Research, 38(3), 145–152.
48.
Yildirim,F. B., Ozsoy,O., Tanriover,G., Kaya,Y., Ogut,E., Gemici,B., Dilmac,S., Ozkan,A., Agar,A., Aslan,M. (2014). Mechanism of the beneficial effect of melatonin in experimental Parkinson’s disease. Neurochemistry International, 79, 1–11.
