Neurobiology of Sleep Disturbances in Neurodegenerative Disorders

ArticleinCurrent pharmaceutical design 14(32):3430-45 · February 2008with11 Reads
DOI: 10.2174/138161208786549353 · Source: PubMed
This review presents sleep disturbances and their underlying pathophysiology in three categories of neurodegenerative disorders namely tauopathies, synucleinopathies, and Huntington's disease (HD) and prion-related diseases. Sleep abnormalities are a major and early feature of neurodegenerative disorders, especially for synucleinopathies, HD and prion-related diseases, in which the sleep-related brainstem regions are severely altered and impaired sooner than in most of the tauopathies. In synucleinopathies, HD and prion-related diseases, specific sleep disturbances, different from those observed in tauopathies, are considered as core manifestations of the disease and in some cases, as preclinical signs. For this reason, the evaluation of sleep components in these neurodegenerative disorders may be useful to make a diagnosis and to assess the efficacy of pharmacotherapy. Since sleep disruption may occur early in the course of neurodegeneration, sleep disturbance may serve as groundwork to study the efficacy of neuroprotective agents to prevent or delay the development of a full-blown neurodegenerative disorder. The cause of sleep disturbances in neurodegenerative disorders may be attributed to several factors, including age-related modifications, symptoms of the disease, comorbid conditions and the neurodegenerative process itself.
    • "Specifically, its diagnostic utility must be characterized beyond its ability to distinguish between otherwise healthy Ab +/À older adults. For example, while sleep disturbance is present among many other psychiatric and neurological conditions [5,62], it remains unclear to what degree this selective <1 Hz NREM SWA disturbance is also present. Targeted examinations in a variety of clinical populations will ultimately determine the accuracy of sleep EEG for differential Box 3. The Role of Orexin in AD The hypothalamic orexin system contributes to the regulation of sleep and wake states. "
    [Show abstract] [Hide abstract] ABSTRACT: Sleep disruption appears to be a core component of Alzheimer's disease (AD) and its pathophysiology. Signature abnormalities of sleep emerge before clinical onset of AD. Moreover, insufficient sleep facilitates accumulation of amyloid-β (Aβ), potentially triggering earlier cognitive decline and conversion to AD. Building on such findings, this review has four goals: evaluating (i) associations and plausible mechanisms linking non-rapid-eye-movement (NREM) sleep disruption, Aβ, and AD; (ii) a role for NREM sleep disruption as a novel factor linking cortical Aβ to impaired hippocampus-dependent memory consolidation; (iii) the potential diagnostic utility of NREM sleep disruption as a new biomarker of AD; and (iv) the possibility of sleep as a new treatment target in aging, affording preventative and therapeutic benefits.
    Full-text · Article · Jun 2016
    • "Sleep fragmentation (SF) and other aspects of impaired sleep architecture are seen in animal models as well as in humans, including obesity (He et al., 2015) and neuroinflammation (He et al., 2014c; Krueger, 2008). Sleep disruption, particularly sleep apnea, is associated with neurodegenerative diseases (Gagnon et al., 2008; Pan & Kastin, 2014). Most recently, Chen et al. showed that the cerebellar cortices of mice receiving lentiviral injection of EGFP-LC3 show a circadian oscillation of the number, volume and signal intensity per cell of the EGFP-LC3 vesicles, higher during the light span and lower in the dark span, starting to decrease around 4 pm but not associated with feeding behavior (Chen et al., 2015). "
    [Show abstract] [Hide abstract] ABSTRACT: Autophagy is essential for normal cellular survival and activity. Circadian rhythms of autophagy have been studied in several peripheral organs but not yet reported in the brain. Here, we measured the circadian rhythm of autophagy-related proteins in mouse hippocampus and tested the effect of sleep fragmentation (SF). Expressions of the autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3) and beclin were determined by western blotting and immunohistochemistry. Both the hippocampal LC3 signal and the ratio of its lipid-conjugated form LC3-II to its cytosolic form LC3-I showed a 24 h rhythm. The peak was seen at ZT6 (1 pm) and the nadir at ZT16 (1 am). The LC3 immunoreactivity in hippocampal CA1 pyramidal neurons also distributed differently, with more diffuse cytoplasmic appearance at ZT16. Chronic SF had a mild effect to disrupt the 24 h rhythm of LC3 and beclin expression. Interestingly, a greater effect of SF was seen after 24 h of recovery sleep when LC3-II expression was attenuated at both the peak and trough of circadian activities. Overall, the results show for the first time that the hippocampus has a distinct rhythm of autophagy that can be altered by SF.
    Full-text · Article · Apr 2016
    • "It is expressed more in the preterm babies and in those born immature [17, 18], suggesting that REMS has a role in brain development and maturity [19, 20]. The quantity of REMS has been found to be affected in most of the diseases from simple fever to complex psycho-somatic disorders [21][22][23][24]. Experimental REMS loss has been reported to affect psycho-somatic behaviour including memory consolidation [25][26][27][28][29], irritability, concentration, mood and behaviour [8, 30]. "
    [Show abstract] [Hide abstract] ABSTRACT: Rapid eye movement sleep (REMS) is naturally expressed at least in all the mammals, including humans, studied so far. It is regulated by interplay among complex neuronal circuitry in the brain involving various neurotransmitters. Although the precise function and role of REMS is yet to be deciphered, loss of REMS increases brain excitability; however, the mechanism of action was unknown. As Na-K ATPase is the key molecule that maintains ionic homeostasis across neuronal membrane and modulates the excitability status of neurons, we proposed that REMS deprivation (REMSD) could affect the neuronal Na-K ATPase activity. On the other hand, evidences suggest that REMSD would elevate noradrenaline (NA) level in the brain and it has been proposed that REMS maintains brain NA at an optimum level. Therefore, while attempting to understand and explain the mechanism of action we hypothesized that REMSD-induced elevated NA could modulate Na-K ATPase activity in the brain and thus modulates the neuronal and brain excitability. In this chapter first we discuss the mechanism of increase in NA level in the brain after REMSD. Then we discuss the effect of such elevated NA on neuronal and glial Na-K ATPase activity. We observed that REMSD-induced increase in NA affected neuronal and glial Na-K ATPase activities in opposite manner, while it increased neuronal Na-K ATPase, and it decreased the same in glia. An intricate regulation of Na-K ATPase activity in neurons and glia is likely to be responsible for maintenance of ionic homeostasis in the brain during normal situation, which when disturbed including upon REMS loss patho-physiological changes and symptoms are expressed.
    Chapter · Dec 2015 · Chronobiology International
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