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![Neuroanatomy of wake promoting nuclei (A) and REM controlling nuclei (B). Sleep promoting nuclei are not shown here; for a review of neurobiology controlling sleep and wake states, see [137]. A: Several monoaminergic nuclei from the pons and midbrain (green) are involved in arousal including the locus coeruleus (LC), parabrachial nucleus (PB), precoeruleus area (PC), dorsal raphe nuclei (DR), ventral periaqueductal gray matter (vPAG), and tuberomammillary nucleus (TMN). In addition, cholinergic nuclei (light blue), particularly from the lateral dorsal tegmentum (LDT) and pedunculopontine tegmentum (PPT), contribute to the alerting signal. This system is further augmented by cholinergic signal from the basal forebrain (BF), and orexinergic neurons from the lateral hypothalamus (dark blue) stabilize wakefulness and inhibit REM sleep. Brainstem pathology affecting wake promoting nuclei within the midbrain or pons can lead to sleep–wake disruption such as hypersomnia and insomnia. B: REM-generator neurons in the pons and midbrain (red) include the sublaterodorsal nucleus (SLD) and precoeruleus region (PC). These regions have ascending projections to the basal forebrain (BF) that promote a dreaming state and descending projections to the medulla and spine that promote muscle atonia. Disruption of these areas, particularly involving descending projections, may cause REM sleep without atonia and REM sleep behavior disorder. Figure modified with permission from Saper CB et al., Neuron, 2010 [138]](publication/362195647/figure/fig1/AS:1183008442847237@1659062600613/Neuroanatomy-of-wake-promoting-nuclei-A-and-REM-controlling-nuclei-B-Sleep-promoting.png)
Neuroanatomy of wake promoting nuclei (A) and REM controlling nuclei (B). Sleep promoting nuclei are not shown here; for a review of neurobiology controlling sleep and wake states, see [137]. A: Several monoaminergic nuclei from the pons and midbrain (green) are involved in arousal including the locus coeruleus (LC), parabrachial nucleus (PB), precoeruleus area (PC), dorsal raphe nuclei (DR), ventral periaqueductal gray matter (vPAG), and tuberomammillary nucleus (TMN). In addition, cholinergic nuclei (light blue), particularly from the lateral dorsal tegmentum (LDT) and pedunculopontine tegmentum (PPT), contribute to the alerting signal. This system is further augmented by cholinergic signal from the basal forebrain (BF), and orexinergic neurons from the lateral hypothalamus (dark blue) stabilize wakefulness and inhibit REM sleep. Brainstem pathology affecting wake promoting nuclei within the midbrain or pons can lead to sleep–wake disruption such as hypersomnia and insomnia. B: REM-generator neurons in the pons and midbrain (red) include the sublaterodorsal nucleus (SLD) and precoeruleus region (PC). These regions have ascending projections to the basal forebrain (BF) that promote a dreaming state and descending projections to the medulla and spine that promote muscle atonia. Disruption of these areas, particularly involving descending projections, may cause REM sleep without atonia and REM sleep behavior disorder. Figure modified with permission from Saper CB et al., Neuron, 2010 [138]
Source publication
Purpose of Review
To comprehensively summarize the sleep pathologies associated with movement disorders, focusing on neurodegenerative diseases.
Recent Findings
Mounting evidence has further implicated both sleep and circadian disruption in the pathophysiology of many movement disorders. In particular, recent data illuminate the mechanisms by whic...
Citations
... In this context, it is well known that the daily rhythm has a great influence on the regulation of cellular homeostasis and physiology (Godinho-Silva et al., 2019;Huang et al., 2011;Kinouchi & Sassone-Corsi, 2020;Kon et al., 2017;Serin & Acar Tek, 2019), and persistent disruptions in its normal functioning could be behind different pathologies (e.g., McEwen & Karatsoreos, 2015), for instance those related to psychopathologies such as major depressive disorder (e.g., Bedrosian & Nelson, 2017;Homolak et al., 2018;Leng et al., 2019;Sato et al., 2022) and/or neurodegeneration (Duncan, 2020;Maiese, 2021;Sharma et al., 2021;Standlee & Malkani, 2022;Wang & Li, 2021). Therefore, the oscillations over time of certain biomarkers such as FADD might be playing a crucial role in maintaining health and/or in the development of these pathologies. ...
Fas‐Associated protein with Death Domain (FADD), a key molecule controlling cell fate by balancing apoptotic versus non‐apoptotic functions, is dysregulated in post‐mortem brains of subjects with psychopathologies, in animal models capturing certain aspects of these disorders, and by several pharmacological agents. Since persistent disruptions in normal functioning of daily rhythms are linked with these conditions, oscillations over time of key biomarkers, such as FADD, could play a crucial role in balancing the clinical outcome. Therefore, we characterized the 24‐h regulation of FADD (and linked molecular partners: p‐ERK/t‐ERK ratio, Cdk‐5, p35/p25, cell proliferation) in key brain regions for FADD regulation (prefrontal cortex, striatum, hippocampus). Samples were collected during Zeitgeber time (ZT) 2, ZT5, ZT8, ZT11, ZT14, ZT17, ZT20, and ZT23 (ZT0, lights‐on or inactive period; ZT12, lights‐off or active period). FADD showed similar daily fluctuations in all regions analyzed, with higher values during lights off, and opposite to p‐ERK/t‐ERK ratios regulation. Both Cdk‐5 and p35 remained stable and did not change across ZT. However, p25 increased during lights off, but exclusively in striatum. Finally, no 24‐h modulation was observed for hippocampal cell proliferation, although higher values were present during lights off. These results demonstrated a clear daily modulation of FADD in several key brain regions, with a more prominent regulation during the active time of rats, and suggested a key role for FADD, and molecular partners, in the normal physiological functioning of the brain's daily rhythmicity, which if disrupted might participate in the development of certain pathologies.
... There are also disturbances in REM activity patterns. These problems may be associated with progressive damage to the brain structures controlling sleep and wakefulness, circadian rhythm disorders, and motor behavior [43,44]. Circadian rhythm disorders and poor quality of sleep intensify pathophysiological changes in the brain [45]. ...
Life is the highest form of adaptation to the environment which is based on energy metabolism. To maintain life, the neuromuscular system must constantly interact with the environment. The striatal muscles are the main energy consumer and their access to energy fuel is mainly limited by the brain’s needs. In the state of wakefulness, the brain must continuously process streams of sensory signals and respond to them with motor actions. At the same time, the brain to be efficient must memorize the sensory-movement relationships. Brain memory networking requires additional energy allocation, and due to limited systemic energy resources, the processes of memorization are completed during the sleep phase when the inactive muscular system allows allocating the energy fuel to the brain functions such as memory trace formation and the removal of the activity-dependent waste products. Both physiological processes can be completed during sleep only, and consequently, chronic sleep disorder leads to pathological changes in brain functioning and escalation of neurodegenerative processes. Consequently, sleep disorders become the main cause of dementia which is the prodrome of Alzheimer’s disease.
... In patients with concurrent insomnia/sleep-wake disorder, the use of levodopa controlled-release, long-acting dopamine agonist (rotigotine transdermal patch, etc.) or sleep hygiene consultation may be related to an excessive daytime sleepiness/sleep attack. With clarification for the cause of excessive daytime sleepiness, the patient develops drowsiness after each dose of dopamine agonist [13]. Additionally, depression, insomnia, or obstructive sleep apnea disorders may still be induced in the conditions, while modafinil is normally used. ...
Parkinson’s disease (PD) is a neurodegenerative disorder with motor deficits due to nigrostriatal dopamine depletion and with the non-motor/premotor symptoms (NMS) such as anxiety, cognitive dysfunction, depression, hyposmia, and sleep disorders. NMS is presented in at least one-fifth of the patients with PD. With the histological information being investigated, stem cells are shown to provide neurotrophic supports and cellular replacement in the damaging brain areas under PD conditions. Pathological change of progressive PD includes degeneration and loss of dopaminergic neurons in the substantia nigra of the midbrain. The current stem cell beneficial effect addresses dopamine boost for the striatal neurons and gliovascular mechanisms as competing for validated PD drug targets. In addition, there are clinical interventions for improving the patient’s NMS and targeting their autonomic dysfunction, dementia, mood disorders, or sleep problems. In our and many others’ research using brain injury models, multipotent mesenchymal stromal cells demonstrate an additional and unique ability to alleviate depressive-like behaviors, independent of an accelerated motor recovery. Intranasal delivery of the stem cells is discussed for it is extensively tested in rodent animal models of neurological and psychiatric disorders. In this review, we attempt to discuss the repairing potentials of transplanted cells into parkinsonism pathological regions of motor deficits and focus on preventive and treatment effects. From new approaches in the PD biological therapy, it is believed that it can as well benefit patients against PD-NMS.
... The incidence and prevalence of sleep disorders continues to in older persons, especially those with neurodegenerative diseases. A recent study clarified the mechanisms of neurodegeneration exacerbated by poor sleep quality and circadian rhythm disorders (Standlee and Malkani, 2022). Small vessel disease exists in both Parkinson's and Alzheimer's diseases (Paolini Paoletti et al., 2021); this refers to the dominant injury of arterioles and capillaries, resulting in reduced or interrupted perfusion of the affected organs, primarily affecting organs that receive most of the cardiac output, such as the brain, kidney, and retina (Hakim, 2019). ...
Objective
The purpose of this study was to examine the current state of the application of imaging in sleep research in degenerative disease, as well as hotspots and trends.
Materials and methods
A search was conducted on the Web of Science Core Collection (WoSCC) between 1 September 2012, and 31 August 2022 for literature related to sleep imaging. This study analyzed 7,679 articles published in this field over the past 10 years, using CiteSpace to analyze tendencies, countries, institutions, authors, and hotspots.
Results
There were 7,679 articles on the application of imaging to sleep research published by 566 institutions located in 135 countries in 1,428 journals; the number of articles was increasing on a yearly basis. According to keyword analysis, the research direction of the application of imaging in sleep research focused on the effects of degenerative diseases on sleep, such as Parkinson’s disease, Alzheimer’s disease, and small vessel disease. A literature evaluation found that Parkinson’s disease, insomnia, sleep quality, and rapid eye movement sleep behavior disorder were the top research trends in this field.
Conclusion
A growing body of research has focused on sleep disorders caused by degenerative diseases. In the application of imaging to sleep research, magnetic resonance functional brain imaging represents a reliable research method. In the future, more aging-related diseases may be the subject of sleep-related research, and imaging could provide convenient and reliable evidence in this respect.
... Poor sleep quality and circadian dysfunction can exacerbate neurodegeneration [123]. Sleep deprivation leads to cognitive deficits in domains including executive function, attention, and processing speed, as well as affective disturbances such as impulsivity and emotional lability [124]. ...
According to Alzheimer’s Disease International, 55 million people worldwide are living with dementia. Dementia is a disorder that manifests as a set of related symptoms, which usually result from the brain being damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, usually accompanied by emotional problems, difficulties with language, and decreased motivation. The most common variant of dementia is Alzheimer’s disease with symptoms dominated by cognitive disorders, particularly memory loss, impaired personality, and judgmental disorders. So far, all attempts to treat dementias by removing their symptoms rather than their causes have failed. Therefore, in the presented narrative review, I will attempt to explain the etiology of dementia and Alzheimer’s disease from the perspective of energy and cognitive metabolism dysfunction in an aging brain. I hope that this perspective, though perhaps too simplified, will bring us closer to the essence of aging-related neurodegenerative disorders and will soon allow us to develop new preventive/therapeutic strategies in our struggle with dementia, Alzheimer’s disease, and Parkinson’s disease.
Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM2.5), including combustion and friction ultrafine PM (UFPM) and industrial nanoparticles (NPs) starting in utero, are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Aβ1 − 42), α-synuclein (α syn) and TAR DNA-binding protein 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic and natural sources and NPs enter the brain through the nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, and placental barriers. On a global scale, the most important sources of outdoor UFPM are motor traffic emissions. This study focuses on the neuropathology heterogeneity and overlap of AD, PD, FTLD, and ALS in older adults, their similarities with the neuropathology of young, highly exposed urbanites, and their strong link with sleep disorders. Critical information includes how this UFPM and NPs cross all biological barriers, interact with brain soluble proteins and key organelles, and result in the oxidative, endoplasmic reticulum, and mitochondrial stress, neuroinflammation, DNA damage, protein aggregation and misfolding, and faulty complex protein quality control. The brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority.
Background:
Quadruple aberrant hyperphosphorylated tau, amyloid-β, α-synuclein, and TDP-43 pathology had been documented in 202/203 forensic autopsies in Metropolitan Mexico City ≤40-year-olds with high exposures to ultrafine particulate matter and engineered nanoparticles. Cognition deficits, gait, equilibrium abnormalities, and MRI frontal, temporal, caudate, and cerebellar atrophy are documented in young adults.
Objective:
This study aimed to identify an association between falls, probable Rapid Eye Movement Sleep Behavior Disorder (pRBD), restless leg syndrome (RLS), and insomnia in 2,466 Mexican, college-educated volunteers (32.5±12.4 years).
Methods:
The anonymous, online study applied the pRBD and RLS Single-Questions and self-reported night-time sleep duration, excessive daytime sleepiness, insomnia, and falls.
Results:
Fall risk was strongly associated with pRBD and RLS. Subjects who fell at least once in the last year have an OR = 1.8137 [1.5352, 2.1426] of answering yes to pRBD and/or RLS questions, documented in 29% and 24% of volunteers, respectively. Subjects fell mostly outdoors (12:01 pm to 6:00 pm), 43% complained of early wake up hours, and 35% complained of sleep onset insomnia (EOI). EOI individuals have an OR of 2.5971 [2.1408, 3.1506] of answering yes to the RLS question.
Conclusion:
There is a robust association between falls, pRBD, and RLS, strongly suggesting misfolded proteinopathies involving critical brainstem arousal and motor hubs might play a crucial role. Nanoparticles are likely a significant risk for falls, sleep disorders, insomnia, and preventable neurodegenerative lethal diseases, thus characterizing air particulate pollutants' chemical composition, emission sources, and cumulative exposure concentrations are strongly recommended.
