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

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 alpha-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.

Fig. 1.

Shows some of the neural circuitry in the brainstem, which we believe acts to regulate sleep motor activity. The frontal sections on the upper left show areas of the rostroventral midbrain (RVMD, dark gray area) and ventral mesopontine junction (VMPJ, light gray area). The RVMD includes the ventral mesencephalic reticular formation (MRF), the dopaminergic nuclei of the substantia nigra (SN) pars compacta and reticulata, the rostral part of the ventral tegmental area (VTA), and the retrorubral nucleus (RR). The ventral mesopontine junction (VMPJ) includes the caudal part of the VTA, RR, and MRF, as well as the rostroventral part of the paralemniscal tegmental field (FTP) of the pons. The sagittal sections shown on the bottom and left sides illustrate projections from the RVMD, VMPJ, pontine inhibitory area (PIA), and nucleus magnocellularis (NMC). Neurons in the RVMD project to the basal ganglia (124) and basal forebrain (125,126) However, the existence of an axonal projection from the VMPJ to the LC remains unclear, as does the transmitter phenotype of this projection and the projection between the VMPJ and NMC. Abbreviations: AQ, aqueduct; DH, dorsal horn; IC, inferior colliculus; IO, inferior olive; LC, locus coeruleus; P, pyramidal tract; PAG, periaqueductal gray; PG, pontine gray; R, red nucleus; SC, superior colliculus; TR, tegmental reticular nucleus; VH, ventral horn; 3, oculomotor nucleus; 6, abducens nucleus.

Fig. 2.

Percentage of time spent in each state during the 24-h recording period before and after RVMD lesion. A significant change in each sleep-wake state occurred on d 3 post-NMDA-RVMD lesion. All stages of the sleep-wake cycle except S1 remained statistically different from the baseline control value over the entire 4-mo period of the experiment. *: p < 0.05; **: p < 0.01; ***: p < 0.001. (From: Lai et al. [1999] Neuroscience 90, 469–483.)