A Review of Sleep and Its Disorders in Patients with Parkinson's Disease in Relation to Various Brain Structures

Abstract

Sleep is an indispensable normal physiology of the human body fundamental for healthy functioning. It has been observed that Parkinson's disease (PD) not only exhibits motor symptoms, but also non-motor symptoms such as metabolic irregularities, altered olfaction, cardiovascular dysfunction, gastrointestinal complications and especially sleep disorders which is the focus of this review. A good understanding and knowledge of the different brain structures involved and how they function in the development of sleep disorders should be well comprehended in order to treat and alleviate these symptoms and enhance quality of life for PD patients. Therefore it is vital that the normal functioning of the body in relation to sleep is well understood before proceeding on to the pathophysiology of PD correlating to its symptoms. Suitable treatment can then be administered toward enhancing the quality of life of these patients, perhaps even discovering the cause for this disease.

Keywords: Parkinson's disease (PD); REMS behavior disorder (RBD); dopamine; hypocretin; non-rapid eye movement sleep (NREMS); rapid eye movement sleep (REMS); sleep; suprachiasmatic nucleus (SCN).

Figure 1

The Suprachiasmatic Nucleus (Adapted and published under the Creative Commons Attribution-Share Alike 3.0 Unported license).

Figure 2

The ARAS: VLPO, ventrolateral pre-optic nucleus; PeF, perifornical area; ORX, orexin; TMN, tuberomamillary nucleus; SN, substantia nigra; VTA, ventral tegmental area; DRN, dorsal raphe nuclei; SE, serotonin; LDT, laterodorsal tegmental nucleus; vlPAG, ventrolateral periaqueductal gray; PPN, pedunculopontine nucleus; LC, locus coeruleus; NE, norepinephrine. Green lines depict the first pathway, and pink lines depict the second pathway. (Adapted and published under the Creative Commons Attribution-Share Alike 3.0 Unported license).

Figure 3

Model depicting reciprocal interactions between sleep and wake promoting structures in the brain: VLPO, ventrolateral pre-optic nucleus; eVLPO, extended VLPO; ORX, orexin; TMN, tuberomamillay nucleus; LC, locus coeruleus; DRN, dorsal raphe nuclei, PPN, pedunculopontine nucleus; LDT, laterodorsal tegmental nucleus; SLD, sublaterodorsal nucleus; Gal, galanine; GABA, gamma-aminobutyric acid; NE, norepinephrine; SE, serotonin; His, histamine, Glu, glutamate. (Saper et al., 2001).

Figure 4

Network model depicting REMS onset: DPGi, dorsal paragigantocellular reticular nucleus; dDpMe, dorsal deep mesenphalic reticular nucleus; DRN, dorsal raphe nucleus; GiV, ventral gigantocellular reticular nucleus; Hcrt, (orexin)-containing neurons; LC, locus coeruleus; vlPAG, ventrolateral periaqueductal gray; SLD, sublaterodorsal nucleus.

Figure 5

The Retino-Hypothalamo-Pineal (RHP) Pathway (depicted by pink dotted lines): The retinohypothalamic tract (RHT) (green dotted line) is the first segment of the RHP pathway, which connects the eye to the hypothalamus. Photons activate melanopsin-expressing retinal ganglion cells (mRGC) which project through the optic nerve to 2nd order neurons in the SCN. SCN neurons then project to 3rd order neurons in the paraventricular nucleus (PVN) of the hypothalamus. These neurons further project to 4th order preganglionic sympathetic neurons in intermediolateral zone of the thoracic lateral horns of the spinal cord. These neurons then project to 5th order postganglionic neurons in the superior cervical ganglia, which then project to 6th order cells (pinealocytes) in the pineal gland, thus making the neurohormone melatonin (Adapted and published under the Creative Commons Attribution-Share Alike 3.0 Unported license).

Figure 6

Flip-flop switch model of sleep-wake regulation between VLPO sleep-promoting and arousal structures neurons (Saper et al., 2005).

Figure 7

Flow chart showing relationship between brain structures governing cortical arousal: CREB (cAMP-response element binding protein) mediates cortical arousal when prompted by NE signals from the LC.

Figure 8

Key brain structures affected by Lewy bodies, Lewy neuritis, and neuronal loss n Parkinson's disease (highlighted in red box): SN, substantia nigra; DRN, dorsal raphe nuclei; vlPAG, ventrolateral periaqueductal gray; LDT, laterodorsal tegmental nucleus; PPN, pedunculopontine nucleus; LC, locus coeruleus; SLD, sublaterodorsal nucleus; MCRF, magnocellular reticular formation. (Adapted and published under the Creative Commons Attribution-Share Alike 3.0 Unported license).

Figure 9

Key brain structures affected by Lewy bodies, Lewy neuritis, and neuronal loss n Parkinson's disease (highlighted in red box): SN, substantia nigra; DRN, dorsal raphe nuclei; vlPAG, ventrolateral periaqueductal gray; LDT, laterodorsal tegmental nucleus; PPN, pedunculopontine nucleus; LC, locus coeruleus; SLD, sublaterodorsal nucleus; MCRF, magnocellular reticular formation. REMS onset occurs when a certain balance is reached between REMS-on and off neurons as well as inhibitory and excitatory pathways within the different brain structures. Damage and degeneration to these brain structures and their relationships lead to RBD. (Adapted and published under the Creative Commons Attribution-Share Alike 3.0 Unported license).