Skip to main content
SpringerLink
Log in

Physiological and anatomical link between parkinson-like disease and REM sleep behavior disorder

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease that is caused by a loss of neurons in the ventral midbrain. Parkinsonian patients often experience insomnia, parasomnias, and daytime somnolence. REM sleep behavior disorder (RBD) is characterized by vigorous movements during REM sleep, and may also be caused by neuronal degeneration in the central nervous system (CNS); however, the site of degeneration remains unclear. Both Parkinsonism and RBD become more prevalent with aging, with onset usually occurring in the sixties. Recent findings show that many individuals with RBD eventually develop Parkinsonism. Conversely, it is also true that certain patients diagnosed with Parkinsonism subsequently develop RBD. Postmortem examination reveals that Lewy bodies, Lewy neurites, and α-synuclein are found in brainstem nuclei in both Parkinsonism and RBD patients. In this article, we will discuss evidence that Parkinsonism and RBD are physiologically and anatomically linked, based on our animal experiments and other studies on human patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. German D. C., Dubach M., Askari S., Apeciale S. G., and Bowden D. M. (1988) 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonian syndrome in Macaca fascicularis: which midbrain dopaminergic neurons are lost? Neuroscience 24, 161–174.

    PubMed  CAS  Google Scholar 

  2. Janowsky A., Vocci F., Berger P., Angel I., Zelnik N., Kleinman J. E., et al. (1987) [3H]GBR-12935 binding to the dopamine transporter is decreased in the caudate nucleus in Parkinson’s disease. J. Neurochem. 49, 617–621.

    PubMed  CAS  Google Scholar 

  3. Lee C. S., Samii A., Sossi V., Ruth T. J., Schulzer M., Holden J. E., et al. (2000) In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease. Ann. Neurol. 47, 493–503.

    PubMed  CAS  Google Scholar 

  4. Varrone A., Marek K. L., Jennings D., Innis R. B., and Seibyl J. P. (2001) [(123)I]beta-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson’s disease and multiple system atrophy. Mov. Disord. 16, 1023–1032.

    PubMed  CAS  Google Scholar 

  5. Pearce R. K. B., Seeman P., Jellinger K., and Tourtellotte W. W. (1990) Dopamine uptake sites and dopamine receptors in Parkinson’s disease and schizophrenia. Eur. Neurol. 30, Suppl 1, 9–14.

    PubMed  Google Scholar 

  6. Seeman P. and Niznik H. B. (1990) Dopamine receptors and transporters in Parkinson’s disease and schizophrenia. FASEB J. 4, 2737–2744.

    PubMed  CAS  Google Scholar 

  7. Cortes R., Camps M., Gueye B., Probst A., and Palacios J. M. (1989) Dopamine receptors in human: autoradiographic distribution of D1 and D2 sites in Parkinson syndrome of different etiology. Brain Res. 483, 30–38.

    PubMed  CAS  Google Scholar 

  8. Hierholzer J., Cordes M., Venz S., Schelosky L., Harisch C., Richter W., et al. (1998) Loss of dopamine-D2 receptor binding sites in parkinsonian plus syndromes. J. Nucl. Med. 39, 954–960.

    PubMed  CAS  Google Scholar 

  9. Tachibana M., Tanaka K., Hishikawa Y., and Kaneko Z. (1975) A sleep study of acute psychotic states due to alcohol and meprobamate addiction, in Advances in sleep research, Vol 2 (Weitzman E. D., ed.), New York, Spectrum, pp. 177–203.

    Google Scholar 

  10. Schenck C. H., Bundlie S. R., Ettinger M. G., and Mahowald M. W. (1986) Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep 9, 293–308.

    PubMed  CAS  Google Scholar 

  11. Eisensehr I., Linke R., Noachtar S., Schwarz J., Gildehaus F. J., and Tatsch K. (2000) Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson’s disease and controls. Brain 123, 1155–1160.

    PubMed  Google Scholar 

  12. Albin R. L., Koeppe R. A., Chervin R. D., Consens F. B., Wernette K., Frey K. A., et al. (2000) Decreased striatal dopaminergic innervation in REM sleep behavior disorder. Neurology 55, 1410–1412.

    PubMed  CAS  Google Scholar 

  13. Tandberg E., Larsen J. P., and Karlsen K. (1998) A community-based study of sleep disorders in patients with Parkinson’s disease. Mov. Disord. 13, 895–899.

    PubMed  CAS  Google Scholar 

  14. Bergonzi P., Chiurulla C., Gambi D., Mennuni G., and Pinto F. (1975) L-dopa plus dopadecar-boxylase inhibitor. Sleep organization in Parkinson’s syndrome before and after treatment. Acta Neurol. Belg. 75, 5–10.

    PubMed  CAS  Google Scholar 

  15. Kales A., Ansel R. D., Markham C. H., Sharf M. B., and Tan T. I. (1971) Sleep in patients with Parkinson’s disease and normal subjects, prior to and following levodopa administration. Clin. Pharmac. Ther. 12, 397–406.

    CAS  Google Scholar 

  16. Bergonzi P., Chiurulla C., Cianchettti C., and Tempesta E. (1974) Clinical pharmacology as an approach to the study of biochemical sleep mechanisms: The action of L-dopa. Confin. Neurol. 36, 5–22.

    PubMed  CAS  Google Scholar 

  17. Mouret J. (1975) Differences in sleep in patients with Parkinson’s disease. EEG Clin. Neurophysiol. 38, 653–657.

    CAS  Google Scholar 

  18. Foley D. J., Monjan A. A., Brown S. L., Simonsick E. M., Wallace R. B., and Blazer D. G. (1995) Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep 18, 425–432.

    PubMed  CAS  Google Scholar 

  19. Barbar S. I., Enright P. L., Boyle P., Foley D., Sharp D. S., Petrovitch H., et al. (2000) Sleep disturbances and their correlates in elderly Japanese American men residing in Hawaii. J. Gerontol. A Biol. Sci. Med. Sci. 55, 406–411.

    Google Scholar 

  20. Schafer D. and Greulich W. (2000) Effects of parkinsonian medication on sleep. J. Neurol. 247 Suppl 4, 24–27.

    Google Scholar 

  21. Wetter T. C., Collado-Seidel V., Pollmacher T., Yassouridis A., and Trenkwalder C. (2000) Sleep and periodic leg movement patters in drug-free patients with Parkinson’s disease and multiple system atrophy. Sleep 23, 361–367.

    PubMed  CAS  Google Scholar 

  22. Ondo W. G., Dat Vuong K., Khan H., Atassi F., Kwak C., and Jankovic J. (2001) Daytime sleepiness and other sleep disorders in Parkinson’s disease. Neurology 57, 1392–1396.

    PubMed  CAS  Google Scholar 

  23. Fish D. R., Sawyers D., Allen P. J., Blackie J. D., Lee A. J., and Marsden C. D. (1991) The effect of sleep on the dyskinetic movements of Parkinson’s disease, Gilles de la Tourette syndrome, Huntington’s disease, and torsion dystonia. Arch. Neurol. 48, 210–214.

    PubMed  CAS  Google Scholar 

  24. Askenasy J. J. M., Weitzman E. D., and Yahr M. D. (1985) Are periodic movements in sleep a basal ganglia dysfunction? J. Neural Transm. 70, 337–348.

    Google Scholar 

  25. Askenasy J. J. M. (1981) Sleep pattern in extrapyramidal disorders. Int. J. Neurol. 15, 62–76.

    PubMed  CAS  Google Scholar 

  26. Bliwise D. L., Williams M. L., Irbe D., Ansari F. P., and Rye D. B. (1997) Inter-rater reliability for identification of REM sleep in Parkinson’s disease. Sleep 23, 671–676.

    Google Scholar 

  27. Askenasy J. J. M. and Yahr M. D. (1985) Reversal of sleep disturbance in Parkinson’s disease by antiparkinsonian therapy: a preliminary study. Neurology 35, 527–532.

    PubMed  CAS  Google Scholar 

  28. Schenck C. H., Hurwitz T. D., and Mahowald M. W. (1993) REM sleep behavior disorder: an update on a series of 96 patients and a review of the world literature. J. Sleep Res. 2, 224–231.

    PubMed  Google Scholar 

  29. Lapierre O. and Montplaisir J. (1992) Polysomnographic features of REM sleep behavior disorder: development of a scoring method. Neurology 42, 1371–1374.

    PubMed  CAS  Google Scholar 

  30. Schenck C. H. and Mahowald M. W. (1990) Polysomnographic, neurologic, psychiatric, and clinical outcome report on 70 consecutive cases with REM sleep behavior disorder (RBD): sustained clonazepam efficacy in 89.5% of 57 treated patients. Cleveland Clin. J. Med. 57, Suppl S9-S23.

    Google Scholar 

  31. Schenck C. H., Bundlie S. R., Patterson A. L., and Mahowald M. W. (1987) Rapid eye movement sleep behavior disorder. A treatable parasomnia affecting older adults. JAMA 257, 1786–1789.

    PubMed  CAS  Google Scholar 

  32. Sforza E., Zucconi M., Petronelli R., Lugaresi E., and Cirignotta F. (1988) REM sleep behavioral disorders. Eur. Neurol. 28, 295–300.

    PubMed  CAS  Google Scholar 

  33. Olson E. J., Boeve B. F., and Silber M. H. (2000) Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain 123, 331–339.

    PubMed  Google Scholar 

  34. Schenck C. H., Hopwood J., Duncan E., and Mahowald M. W. (1992) Preservation and loss of REM atonia in human idiopathic REM sleep behavior disorder (RBD): quantitative polysomnographic (PSG) analyses in 17 patients. Sleep Res. 21, 16.

    Google Scholar 

  35. Tachibana N., Kimura K., Kitajima K., Shinde A., Kimura J., and Shibasake H. (1997) REM sleep motor dysfunction in multiple system atrophy: with special emphasis on sleep talk as its early clinical manifestation. J. Neurol. Neurosurg. Psychiatry 63, 678–681.

    PubMed  CAS  Google Scholar 

  36. Salva M.A.Q. and Guilleminault C. (1986) Olivopontocerebellar degeneration, abnormal sleep, and REM sleep without atonia. Neurology 36, 576–577.

    PubMed  CAS  Google Scholar 

  37. Tachibana N., Kimura K., Kitajima K., Nagamine T., Kimura J., and Shibasaki H. (1995) REM sleep without atonia at early stage of sporadic olivopontocerebellar atrophy. J. Neurol. Sci. 132, 28–34.

    PubMed  CAS  Google Scholar 

  38. Shimizu T., Inami Y., Sugita Y., Iijima S., Teshima Y., et al. (1990) REM sleep without muscle atonia (Stage 1-REM) and its relation to delirious behavior during sleep in patients with degenerative diseases involving the brain stem. Jpn. J. Psychiatry Neurol. 44, 681–692.

    PubMed  CAS  Google Scholar 

  39. Halliday G. M., Li Y. W., Blumbergs P. C., Joh T. H., Cotton R. G. H., Howe P.R.C., et al. (1990) Neuropathology of immunohistochemically identified brainstem neurons in Parkinson’s disease. Ann. Neurol. 27, 373–385.

    PubMed  CAS  Google Scholar 

  40. Goto S. and Hirano A. (1991) Catecholaminergic neurons in the parabrachial nucleus of normal individuals and patients with idiopathic Parkinson’s disease. Ann. Neurol. 30, 192–196.

    PubMed  CAS  Google Scholar 

  41. Patt S. and Gerhard L. (1993) A golgi study of human locus coeruleus in normal brains and in Parkinson’s disease. Neuropathol. Appl. Neurobiol. 19, 519–523.

    PubMed  CAS  Google Scholar 

  42. Jellinger K. A. (1991) Pathology of Parkinson’s disease. Changes other than the nigrostriatal pathway. Mol. Chem. Neuropathol. 14, 153–197.

    PubMed  CAS  Google Scholar 

  43. Schenck C. H., Garcia-Rill E., Skinner R. D., Anderson M. L., and Mahowald M. W. (1996b) A case of REM sleep behavior disorder with autopsy-confirmed Alzheimer’s disease: postmortem brain stem histochemical analyses. Biol. Psychiatry 40, 422–425.

    PubMed  CAS  Google Scholar 

  44. Lewy F. H. (1912) Paralysis agitans. I. Pathologische anatomie, in Handbuch der neurologie (Lewandowsky M, ed.), Springer, Berlin, pp. 920–933.

    Google Scholar 

  45. Tretiakoff C. (1919) Contribution a l’etude de l’Anatomie pathologique du locus niger de soemmering avec quelques deductions relatives a la pathogenie des troubles du tonus musculaire et de la maladie de Parkinsons. These de Paris.

  46. Kosaka K., Yoshimura M., Ikeda K., and Budka H. (1984) Diffuse type of Lewy body disease: progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree — a new disease? Clin. Neuropathol. 3, 185–192.

    PubMed  CAS  Google Scholar 

  47. Ditter S. M. and Mirra S. S. (1987) Neuropathological and clinical features of Parkinson’s disease in Alzheimer’s disease patients. Neurology 37, 754–760.

    PubMed  CAS  Google Scholar 

  48. Uchiyama M., Isse K., Tanaka K., Yokota N., Hamamoto M., Aida S., et al. (1995) Incidental Lewy body disease in a patient with REM sleep behavior disorder. Neurology 45, 709–712.

    PubMed  CAS  Google Scholar 

  49. Ohama E. and Ikuta F. (1976) Parkinson’s disease: distribution of Lewy bodies and monoamine neuron system. Acta Neuropathol. 34, 311–319.

    PubMed  CAS  Google Scholar 

  50. Forno L. S. (1986) The Lewy body in Parkinson’s disease. Adv. Neurol. 45, 35–43.

    Google Scholar 

  51. Turner R. S., D’Amato C. J., Chervin R. D., and Blaivas M. (2000) The pathology of REM sleep behavior disorder with comorbid Lewy body dementia. Neurology 55, 1730–1732.

    PubMed  CAS  Google Scholar 

  52. Maroteaux L., Campanelli J. T., and Scheller R. H. (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J. Neurosci. 8, 2804–2815.

    PubMed  CAS  Google Scholar 

  53. Spillantini M. G., Growther R. A., Jakes R., Hasegawa M., and Goedert M. (1998) α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA 95, 6469–6473.

    PubMed  CAS  Google Scholar 

  54. Hishikawa A., Hashizume Y., Yoshida M., and Sobue G. (2001) Widespread occurrence of argyrophilic glial inclusions in Parkinson’s disease. Neuropathol. Appl. Neurobiol. 27, 362–372.

    PubMed  CAS  Google Scholar 

  55. Murphy D. D., Rueter S. M., Trojanowski J. Q., and Lee V.M.Y. (2000) Synucleins are developmentally expressed, and α-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J. Neurosci. 20, 3214–3220.

    PubMed  CAS  Google Scholar 

  56. Jensen P. H., Nielsen M. S., Jakes R., Dotti C. G., and Goedert M. (1998) Binding of alphasynuclein to brain vesicles is abolished by familial Parkinson’s disease mutation. J. Biol. Chem. 273, 26,292–26,294.

    CAS  Google Scholar 

  57. Baba M., Nakajo S., Tu P. H., Tomita T., Nakaya K., Lee V. M. Y., et al. (1998) Aggregation of α-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am. J. Pathol. 152, 879–884.

    PubMed  CAS  Google Scholar 

  58. Wakabayashi K., Matsumoto K., Takayama K., Yoshimoto M., and Takahashi H. (1997) NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson’s disease. Neurosci. Lett. 239, 45–48.

    PubMed  CAS  Google Scholar 

  59. Takeda A., Mallory M., Sundsmo M., Honer W., Hansen L., and Masliah E. (1998) Abnormal accumulation of NACP/α-synuclein in neurodegenerative disorders. Am. J. Pathol. 152, 367–372.

    PubMed  CAS  Google Scholar 

  60. Braak H., Rub U., Sandmann-Keil D., Gai W. P., de Vos R. A. I., Jansen E. N. H., et al. (2000) Parkinson’s disease: affection of brain stem nuclei controlling premotor and motor neurons of the somatomotor system. Acta Neuropathol. 99, 489–495.

    PubMed  CAS  Google Scholar 

  61. Braak H., Sandmann-Keil D., Gai W. P., and Braak E. (1999) Extensive axonal Lewy neurites in Parkinson’s disease: a novel pathological feature revealed by α-synuclein immunohistochemistry. Neurosci. Lett. 265, 67–69.

    PubMed  CAS  Google Scholar 

  62. Namura I., Douillet P., Sun G. J., Pert A., Cohen R. M., and Chiueh C. C. (1987) MPP4 (1-methyl-4-phenylpyridine) is a neurotoxin to dopamine-, norepinephrine- and serotonin-containing neurons. Eur. J. Pharmacol. 136, 31–37.

    PubMed  CAS  Google Scholar 

  63. Ballard P. A., Tetrud J. W., and Langston J. W. (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): 7 cases. Neurology 35, 949–956.

    PubMed  CAS  Google Scholar 

  64. Davis G. C., Williams A. C., Markey S. P., Ebert M. H., Caine E. D., Reichert C. M., et al. (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiat. Res. 1, 249–254.

    CAS  Google Scholar 

  65. Forno L. S., Langston J. W., DeLanney L. E., Irwin I., and Ricaurte G. A. (1986) Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann. Neurol. 20, 49–55.

    Google Scholar 

  66. Kowall N. W., Hantrye P., Brouillet E., Beal M. F., McKee A. C., and Ferrante R. J. (2000) MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons. Neuroreport 11, 211–213.

    PubMed  CAS  Google Scholar 

  67. Pungor K., Papp M., Kekesi K., and Juhasz G. (1990) A novel effect of MPTP: the selective suppression of paradoxical sleep in cats. Brain Res. 525, 310–314.

    PubMed  CAS  Google Scholar 

  68. Jouvet M. and Delorme J. F. (1965) Locus coeruleus et sommeil paradoxal. C R Seances Soc. Biol. Fil. 159, 895–899.

    Google Scholar 

  69. Henley K. and Morrison A. R. (1974) A re-evaluation of the effects of lesions of the pontine tegmentum and locus coeruleus on phenomena of paradoxical sleep in the cat. Acta Neurobiol. Exp. 34, 215–232.

    CAS  Google Scholar 

  70. Schenkel E. and Siegel J. M. (1989) REM sleep without atonia after lesions of the medial medulla. Neurosci. Lett. 98, 159–165.

    PubMed  CAS  Google Scholar 

  71. Shouse M. N. and Siegel J. M. (1992) Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep. Brain Res. 571, 50–63.

    PubMed  CAS  Google Scholar 

  72. Holmes C. J. and Jones B. E. (1994) Importance of cholinergic, GABAergic, serotonergic and other neurons in the medial medullary reticular formation for sleep-wake states studied by cytotoxic lesions in the cat. Neuroscience 62, 1179–1200.

    PubMed  CAS  Google Scholar 

  73. Hendricks J. C., Morrison A. R., and Mann G. L. (1982) Different behaviors during paradoxical sleep without atonia depend on pontine lesion site. Brain Res. 239, 81–105.

    PubMed  CAS  Google Scholar 

  74. Schenck C. H. and Mahowald M. W. (1996) REM sleep parasomnias. Neurol. Clin. 14, 697–720.

    PubMed  CAS  Google Scholar 

  75. Lai Y. Y. and Siegel J. M. (1990) Muscle tone suppression and stepping produced by stimulation of midbrain and rostral pontine reticular formation. J. Neurosci. 10, 2727–2734.

    PubMed  CAS  Google Scholar 

  76. Lai Y. Y. and Siegel J. M. (1997) Brainstem-mediated locomotion and myoclonic jerks. I. Neural substrates. Brain Res. 745, 257–264.

    PubMed  CAS  Google Scholar 

  77. Dahlstrom A. and Fuxe K. (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. Acta Physiol. Scand. 62 Suppl. 232, 5–78.

    Google Scholar 

  78. Wiklund L., Leger L., and Persson M. (1981) Monoamine cell distribution in the cat brain stem. A fluorescence histochemical study with quantification of indolaminergic and locus coeruleus cell groups. J. Comp. Neurol. 203, 613–647.

    PubMed  CAS  Google Scholar 

  79. Lai Y. Y., Clements J. R., and Siegel J. M. (1993) Glutamatergic and cholinergic projections to the pontine inhibitory area identified with horseradish peroxidase retrograde transport and immunohistochemistry. J. Comp. Neurol. 336, 321–330.

    PubMed  CAS  Google Scholar 

  80. Ford B., Holmes C. J., Mainville L., and Jones B. E. (1995) GABAergic neurons in the rat pontomesencephalic tegmentum: codistribution with cholinergic and other tegmental neurons projecting to the posterior lateral hypothalamus. J. Comp. Neurol. 363, 177–196.

    PubMed  CAS  Google Scholar 

  81. Stamp J. A. and Semba K. (1995) Extent of colocalization of serotonin and GABA in the neurons of the rat raphe nuclei. Brain Res. 677, 39–49.

    PubMed  CAS  Google Scholar 

  82. Vertes R. P. and Crane A. M. (1997) Distribution, quantification, and morphological characteristics of serotonin-immunoreactive cells of the supralemniscal nucleus (B9) and pontomesencephalic reticular formation in the rat. J. Comp. Neurol. 378, 411–424.

    PubMed  CAS  Google Scholar 

  83. Magoun H. W. and Rhines R. (1946) An inhibitory mechanism in the bulbar reticular formation. J. Neurophysiol. 9, 165–171.

    Google Scholar 

  84. Lai Y. Y., Siegel J. M., and Wilson W. J. (1987) Effect of blood pressure on medial medulla-induced muscle atonia. Am. J. Physiol. 252, H1249-H1257.

    PubMed  CAS  Google Scholar 

  85. Hajnik T., Lai Y. Y., and Siegel J. M. (2000) Atonia-related regions in the rodent pons and medulla. J. Neurophysiol. 84, 1942–1948.

    PubMed  CAS  Google Scholar 

  86. Lai Y. Y. and Siegel J. M. (1991) Pontomedullary glutamate receptors mediating locomotion and muscle tone suppression. J. Neurosci. 11, 2931–2937.

    PubMed  CAS  Google Scholar 

  87. Lai Y. Y. and Siegel J. M. (1992) Corticotropin-releasing factor mediated muscle atonia in pons and medulla. Brain Res. 575, 63–68.

    PubMed  CAS  Google Scholar 

  88. Lai Y. Y. and Siegel J. M. (1997) Brainstem-mediated locomotion and myoclonic jerks. II. Pharmacological effects. Brain Res. 745, 265–270.

    PubMed  CAS  Google Scholar 

  89. Lai Y. Y., Shalita T., Kodama T., and Siegel J. M. (2001) Neurotoxic lesion of the ventral mesopontine junction induces muscle hyperactivity during sleep. Soc. Neurosci. Abstr. Vol 27, Program # 296.2.

  90. Lai Y. Y., Shalita T., Wu J. P., and Siegel J. M. (2002) Neurotoxic lesion of the ventral mesopontine junction induces hypersomnia and muscle hyperactivity during sleep—an animal model of PLMD and RBD. Sleep 25, A62.

  91. Lai Y. Y. and Siegel J. M. (1999) Muscle atonia in REM sleep, in Rapid eye movement sleep. (Mallick B. N. and Inoue S., eds.), Narosa Pub. House, New Delhi, pp. 69–90.

    Google Scholar 

  92. Schneider J. S., Yuwiler A., and Markham C. H. (1986) Production of a Parkinson-like syndrome in the cat with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): behavior, histology, and biochemistry. Exp. Neurol. 91, 293–307.

    PubMed  CAS  Google Scholar 

  93. Understedt U. (1968) 6-hydroxydopamine induced degeneration of central monoamine neurons. Eur. J. Pharmacol. 5, 107–110.

    Google Scholar 

  94. Breese G. R. and Taylor T. D. (1970) Effects of 6-hydroxydopamine on brain norepinephrine and dopamine: evidence for selective degeneration of catecholamine neurons. J. Pharmacol. Exp. Ther. 174, 413–420.

    PubMed  CAS  Google Scholar 

  95. Sawynok J. and Reid A. (1996) Neurotoxin-induced lesions to central serotonergic, noradrenergic and dopaminergic systems modify caffeine-induced antinociception in the formalin test and locomotor stimulation in rats. J. Pharmacol. Exp. Ther. 277, 646–653.

    PubMed  CAS  Google Scholar 

  96. Petitjean F., Laguzzi R., Sordet F., Jouvet M., and Pujol J. F. (1972) Effects de l’injection intraventriculaire de 6-hydroxydopamine. I. Sur les monoamines cerebrales du chat. Brain Res. 48, 281–293.

    PubMed  CAS  Google Scholar 

  97. Laguzzi R., Petitjean F., Pujol J. F., and Jouvet M. (1972) Effects de l’injection intraventriculaire de 6-hydroxydopamine. II Sur le cycle veille-sommeils du chat. Brain Res. 48, 295–310.

    PubMed  CAS  Google Scholar 

  98. Miller J. D., Farber J., Gatz P., Roffwarg H., and German D. C. (1983) Activity of mesencephalic dopamine and non-dopamine neurons across stages of sleep and waking in the rat. Brain Res. 273, 133–141.

    PubMed  CAS  Google Scholar 

  99. Steinfels G. F., Heym J., Strecker R. E., and Jacobs B. L. (1983) Behavioral correlates of dopaminergic unit activity in freely moving cats. Brain Res. 258, 217–228.

    PubMed  CAS  Google Scholar 

  100. Otterson O. P. and Storm-Mathisen J. (1984) Neurons containing or accumulating transmitter amino acids. In: Handbook of chemical neuroanatomy, (Bjoklund A., and Hokfelt T., Kuhar M. J., eds.), Amsterdam: Elsevier, pp. 141–245.

    Google Scholar 

  101. Datta S., Curro Dossi R., Pare D., Oakson G., and Steriade M. (1991) Substantia nigra reticulata neurons during sleep-waking states: relation with ponto-geniculo-occipital waves. Brain Res. 566, 344–347.

    PubMed  CAS  Google Scholar 

  102. Szymusiak R. and McGinty D. (1986) Sleep-related neuronal discharge in the basal forebrain of cats. Brain Res. 258, 217–228.

    Google Scholar 

  103. Nitz D. and Siegel J. S. (1996) GABA release in posterior hypothalamus across sleep-waking cycle. Am. J. Physiol. 271, R1707-R1712.

    PubMed  CAS  Google Scholar 

  104. Lin J. S., Sakai K., Vanni-Mercier G., and Jouvet M. (1989) A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats. Brain Res. 479, 225–240.

    PubMed  CAS  Google Scholar 

  105. Lai Y. Y., Shalita T., Hajnik T., Wu J. P., Kuo J. S., Chia L. G., et al. (1999) Neurotoxic N-methyl-D-aspartate lesion of the ventral midbrain and mesopontine junction alters sleep wake organization. Neuroscience 90, 469–483.

    PubMed  CAS  Google Scholar 

  106. Lai Y. Y., Clements J. R., Wu X. Y., Shalita T., Wu J. P., Kuo J. S., et al. (1999) Brainstem projections to the ventromedial medulla in cat: retrograde transport horseradish peroxidase and immunohistochemical studies. J. Comp. Neurol. 408, 419–436.

    PubMed  CAS  Google Scholar 

  107. Luppi P. H., Aston-Jones G., Akaoka H., Chouvet G., and Jouvet M. (1995) Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and Phaseolus vulgaris Leucoagglutinin. Neuroscience 65, 119–160.

    PubMed  CAS  Google Scholar 

  108. Vertes R. P. and Martin G. F. (1988) Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat. J. Comp. Neurol. 275, 511–541.

    PubMed  CAS  Google Scholar 

  109. Understedt U. and Arbuthnott G. W. (1970) Quantitative recording of rotational behavior in rats after 6-hydroxydopamine lesions of the nigrostriatal doapmine system. Brain Res. 24, 485–493.

    Google Scholar 

  110. Carey R. J. (1986) Relationship of changes in spontaneous motor activity to spontaneous circling in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. Exp. Neurol. 92, 591–600.

    PubMed  CAS  Google Scholar 

  111. Dunbar J. S., Hitchcock K., Latimer M., Rugg E. L., Ward N., and Winn P. (1992) Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II. Examination of eating and drinking, rotation, and reaching and grasping following unilateral ibotenate or quinolinate lesions. Brain Res. 589, 194–206.

    PubMed  CAS  Google Scholar 

  112. Kiyatkin E. A. and Rebec G. V. (1998) Heterogeneity of ventral tegmental area neurons: single-unit recording and iontophoresis in awake, unrestrained rats. Neuroscience 85, 1285–1309.

    PubMed  CAS  Google Scholar 

  113. Gulley J. M., Kuwajima M., Mayhill E., and Rebec G. V. (1999) Behavior-related changes in the activity of substantia nigra pars reticulata neurons in freely moving rats. Brain Res. 845, 68–76.

    PubMed  CAS  Google Scholar 

  114. Kelland M. D. and Asdourian D. (1989) Pedunculopontine tegmental nucleus-induced inhibition of muscle activity in the rat. Behav. Brain Res. 34, 213–234.

    PubMed  CAS  Google Scholar 

  115. Lai Y. Y. and Siegel J. M. (1988) Medullary regions mediating atonia. J. Neurosci. 8, 4790–4796.

    PubMed  CAS  Google Scholar 

  116. Fung S. J. and Barnes C. D. (1981) Evidence of facilitatory coerulospinal action in lumbar motoneurons of cats. Brain Res. 216, 299–311.

    PubMed  CAS  Google Scholar 

  117. Lai Y. Y., Strahlendorf H. K., Fung S. J., and Barnes C. D. (1989) The actions of two monoamines on spinal motoneurons from stimulation of the locus coeruleus in the cat. Brain Res. 484, 268–272.

    PubMed  CAS  Google Scholar 

  118. Lai Y. Y., Kodama T., and Siegel J. M. (2001) Changes in monoamine release in the ventral horn and hypoglossal nucleus linked to pontine inhibition of muscle tone: an in vivo microdialysis study. J. Neurosci. 21, 7384–7391.

    PubMed  CAS  Google Scholar 

  119. Lai Y. Y., Kodama T., and Siegel J. M. (2000) Suppression of norepinephrine release is linked to the rostral dorsomedial but not ventromedial medulla induced atonia. Soc. Neurosci. Abstr. 26, 693.

    Google Scholar 

  120. Kodama T., Lai Y. Y., and Siegel J. M. (2000) Glycine release is increased in the ventral horn and hypoglossal motoneuron pools during rostromedial medulla-induced atonia. Soc. Neurosci. Abstr. 26, 693.

    Google Scholar 

  121. Eisensehr I., v Lindeiner H., Jager M., and Noachtar S. (2001) REM sleep behavior in sleep-disordered patients with versus without Parkinson’s disease: is there a need for polysomnography? J. Neurol. Sci. 186, 7–11.

    PubMed  CAS  Google Scholar 

  122. Schenck C. H., Bundlie S. B., and Mahowald M. W. (1996) Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder. Neurology 46, 388–393.

    PubMed  CAS  Google Scholar 

  123. Sanford L. D., Morrison A. R., Mann G. L., Harris J. S., Yoo L., and Ross R. J. (1994) Sleep pattering and behaviour in cats with pontine lesions creating REM without atonia. J. Sleep Res. 3, 233–240.

    PubMed  Google Scholar 

  124. Lavoie B., Smith Y., and Parent A. (1989) Dopaminergic innervation of the basal ganglia in the squirrel monkey as revealed by tyrosine hydroxylase immunohistochemistry. J. Comp. Neurol. 289, 36–52.

    PubMed  CAS  Google Scholar 

  125. Fallon J. H. and Moore R. Y. (1978) Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J. Comp. Neurol. 180, 545–580.

    PubMed  CAS  Google Scholar 

  126. Vertes R. P. (1988) Brainstem afferents to the basal forebrain in the rat. Neuroscience 24, 907–935.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, School of Medicine, UCLA and Neurobiology Research (151A3) VAGLAHS Sepulveda, 91343, North Hills, CA

    Yuan-Yang Lai & Jerome M. Siegel

Authors
  1. Yuan-Yang Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jerome M. Siegel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuan-Yang Lai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lai, YY., Siegel, J.M. Physiological and anatomical link between parkinson-like disease and REM sleep behavior disorder. Mol Neurobiol 27, 137–151 (2003). https://doi.org/10.1385/MN:27:2:137

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MN:27:2:137

Index Entries

Search

Navigation