Sleep Deprivation and Neurological Disorders

Bishir, Muhammed; Bhat, Abid; Essa, Musthafa Mohamed; Ekpo, Okobi Eko; Ihunwo, Amadi O.; Veeraraghavan, Vishnu Priya; Mohan, Surapaneni Krishna; Mahalakshmi, Arehally M.; Ray, Bipul; Tuladhar, Sunanda; Chang, Sulie L.; Chidambaram, Saravana Babu; Sakharkar, Meena Kishore; Guillemin, Gilles J.; Qoronfleh, M. Walid; Ojcius, David M.

doi:10.1155/2020/5764017

Cited by 124 publications

(100 citation statements)

References 223 publications

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“…In the United States, estimates suggest that nearly 70% of adults and teenagers have insufficient sleep at least one day per month [ 2 – 4 ]. Acute sleep deprivation results in cognitive impairments (reviewed in [ 5 ]), as well as the exacerbation of neuropsychiatric and mood disorders (reviewed in [ 6 , 7 ]). The decrements in cognitive function and performance induced by acute sleep deprivation create an economic burden with decreased workplace productivity as well as increased accident risk encumbering public safety [ 8 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Altered hippocampal transcriptome dynamics following sleep deprivation

et al. 2021

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Widespread sleep deprivation is a continuing public health problem in the United States and worldwide affecting adolescents and adults. Acute sleep deprivation results in decrements in spatial memory and cognitive impairments. The hippocampus is vulnerable to acute sleep deprivation with changes in gene expression, cell signaling, and protein synthesis. Sleep deprivation also has long lasting effects on memory and performance that persist after recovery sleep, as seen in behavioral studies from invertebrates to humans. Although previous research has shown that acute sleep deprivation impacts gene expression, the extent to which sleep deprivation affects gene regulation remains unknown. Using an unbiased deep RNA sequencing approach, we investigated the effects of acute sleep deprivation on gene expression in the hippocampus. We identified 1,146 genes that were significantly dysregulated following sleep deprivation with 507 genes upregulated and 639 genes downregulated, including protein coding genes and long non-coding RNAs not previously identified as impacted by sleep deprivation. Notably, genes significantly upregulated after sleep deprivation were associated with RNA splicing and the nucleus. In contrast, downregulated genes were associated with cell adhesion, dendritic localization, the synapse, and postsynaptic membrane. Furthermore, we found through independent experiments analyzing a subset of genes that three hours of recovery sleep following acute sleep deprivation was sufficient to normalize mRNA abundance for most genes, although exceptions occurred for some genes that may affect RNA splicing or transcription. These results clearly demonstrate that sleep deprivation differentially regulates gene expression on multiple transcriptomic levels to impact hippocampal function.

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Section: Introductionmentioning

confidence: 99%

Altered hippocampal transcriptome dynamics following sleep deprivation

et al. 2021

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“…SD resulted in learning and memory impairments, especially when the hippocampus was required for these learning and memory processes [9]. Furthermore, the immunological and redox system was affected upon SD injury, leading to neuroin ammation and oxidative stress, and the hippocampus was rich in microglia and in ammatory factor receptors which responded to in ammatory reaction [10].…”

Section: Introductionmentioning

confidence: 99%

Activation of the Hippocampal LXRβ Improves Sleep-Deprived Cognitive Impairment by Inhibiting Neuroinflammation

Qiu

Wang

et al. 2021

Mol Neurobiol

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Sleep deprivation (SD) leads to cognitive impairment due to neuroin ammation associated with impaired hippocampal neuronal plasticity and memory processes. Liver X receptors (LXRs), including LXRα and LXRβ isoforms, are crucial for synaptic plasticity as well as anti-in ammation. However, the potential roles of LXRs in the pathogenesis of cognitive impairment induced by SD remain unclear. We revealed that SD resulted in LXRβ reduction in hippocampus, which was associated with upregulated expression of high mobility group box1 (HMGB1)/toll-like receptor 4 (TLR4)/NF-κB p65, and knockdown of hippocampal LXRβ by shRNA (shLXRβ) led to cognitive impairment. GW3965, a dual agonist for both LXRα and LXRβ, ameliorated SD-induced cognitive impairment by inhibiting microglia activation, suppressing HMGB1/TLR4/NF-κB p65 pathway, and ultimately affecting the hippocampal expression of in ammatory cytokines in SD mice. LXRβ knockdown by shLXRβ, abrogated GW3965-mediated the inhibition of HMGB1/TLR4/NF-κB p65 pathway, therefore abolished the cognitive improvement.Moreover, inhibition of HMGB1 by glycyrrhizin (GLY) synergistic promoted GW3965-mediated antiin ammation in activated microglia after LPS/ATP stimulation and facilitated the cognitive improvement after GW administration by activating LXRβ. All the data suggested that GW3965 ameliorated impaired cognition in SD mice by suppressing HMGB1/TLR4/NF-κB p65 pathway followed LXRβ activation. This study correlates a de cit of LXRβ in cognitive dysfunction in SD associated with HMGB1 in ammatory pathway in hippocampus, and LXRs may serve as a potential therapeutic target for cognitive impairment with anti-in ammation.

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“…The orexin receptor antagonist suvorexant might be useful for the prevention and treatment of AD because of its neuroprotective effect, with reduction of β-amyloid plaques and improvement of synaptic plasticity [ 158 ]. At least in part, this effect may result from enhanced sleep-related brain glymphatic clearance of metabolic by-products, such as amyloid-β [ 159 , 160 ]. On the other hand, studies on mouse models show that orexins can ameliorate parkinsonian motor deficits by increasing the spontaneous activation of pallidal neurons [ 161 ].…”

Section: Orexin Cancer and Neurodegenerative Diseasesmentioning

confidence: 99%

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

Mogavero

Silvani

DelRosso

et al. 2021

Cancers

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Conditions such as Alzheimer’s (AD) and Parkinson’s diseases (PD) are less prevalent in cancer survivors and, overall, cancer is less prevalent in subjects with these neurodegenerative disorders. This seems to suggest that a propensity towards one type of disease may decrease the risk of the other. In addition to epidemiologic data, there is also evidence of a complex biological interconnection, with genes, proteins, and pathways often showing opposite dysregulation in cancer and neurodegenerative diseases. In this narrative review, we focus on the possible role played by orexin signaling, which is altered in patients with narcolepsy type 1 and in those with AD and PD, and which has been linked to β-amyloid brain levels and inflammation in mouse models and to cancer in cell lines. Taken together, these lines of evidence depict a possible case of inverse comorbidity between cancer and neurodegenerative disorders, with a role played by orexins. These considerations suggest a therapeutic potential of orexin modulation in diverse pathologies such as narcolepsy, neurodegenerative disorders, and cancer.

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Sleep Deprivation and Neurological Disorders

Cited by 124 publications

References 223 publications

Altered hippocampal transcriptome dynamics following sleep deprivation

Altered hippocampal transcriptome dynamics following sleep deprivation

Activation of the Hippocampal LXRβ Improves Sleep-Deprived Cognitive Impairment by Inhibiting Neuroinflammation

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

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