Sleeping Sickness Disrupts the Sleep-Regulating Adenosine System

Rijo‐Ferreira, Filipa; Bjorness, Theresa E.; Cox, Kimberly; Sonneborn, Alex; Greene, Robert; Takahashi, Joseph S.

doi:10.1523/jneurosci.1046-20.2020

Cited by 15 publications

(12 citation statements)

References 67 publications

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“…Circadian rhythms can be modulated by temperature, nutrition, immune challenges, social interactions, and mechanosensory stimulation, among other factors [22][23][24][25][26]. Similarly, the sleep homeostat and its response to sleep deprivation can be affected by stress, social cues, and infections [27][28][29]. Process C and Process S are separable, but there is evidence of interaction between them [6].…”

Section: Introductionmentioning

confidence: 99%

Many faces of sleep regulation: beyond the time of day and prior wake time

2021

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The two‐process model of sleep regulation posits two main processes regulating sleep: the circadian process controlled by the circadian clock and the homeostatic process that depends on the history of sleep and wakefulness. The model has provided a dominant conceptual framework for sleep research since its publication ~ 40 years ago. The time of day and prior wake time are the primary factors affecting the circadian and homeostatic processes, respectively. However, it is critical to consider other factors influencing sleep. Since sleep is incompatible with other behaviors, it is affected by the need for essential behaviors such as eating, foraging, mating, caring for offspring, and avoiding predators. Sleep is also affected by sensory inputs, sickness, increased need for memory consolidation after learning, and other factors. Here, we review multiple factors influencing sleep and discuss recent insights into the mechanisms balancing competing needs.

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Section: Introductionmentioning

confidence: 99%

Many faces of sleep regulation: beyond the time of day and prior wake time

2021

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“…T . b. rhodesiense infections are known to disrupt the circadian rhythm which results in sleep disturbance in infected individuals (4, 22-24). For this, we observed that circadian rhythm CIPC ( clock interacting pacemaker ) was differentially expressed (padj<1.59E-6) and down regulated (log2FC -1.9) suggesting a disruption of circadian rhythm in patients with stage 1 disease compared to healthy individuals.…”

Section: Resultsmentioning

confidence: 99%

Distinct Differences in Gene Expression Profiles in Early and Late Stage Rhodesiense HAT Individuals in Malawi

Nambala

Mulindwa

Noyes

et al. 2022

Preprint

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T. b. rhodesiense is the causative agent of rhodesian Human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between the different foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected with T. b. rhodesiense was used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease focus. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 25 healthy controls and 23 r-HAT case samples of which 3 case samples were excluded for downstream analysis as outliers. 4519 genes were significantly differentially expressed (p adjusted <0.05) in individuals with early stage 1 r-HAT disease (n = 12) and 1824 genes in individuals with late stage 2 r-HAT disease (n = 8). Enrichment of innate immune response genes through neutrophil activation was identified in individuals with both early and late stages of the disease. Additionally, lipid metabolism genes were enriched in late stage 2 disease. We further identified uniquely upregulated genes (log2 Fold Change 1.4 - 2.0) in stage 1 (ZNF354C) and stage 2 (TCN1 and MAGI3) blood. Our data brings new insight into the human transcriptome landscape during T. b. rhodesiense infection. We have further identified key biological pathways and transcripts during stage 1 and stage 2 r-HAT. Lastly, we have identified potential diagnostic biomarkers that may be used for staging of r-HAT disease.

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“…Another target gene that we identified in the present study was ADORA1 , which regulates various biological functions, including the mechanisms underlying sleep [ 101 , 102 ], and psychiatric disorders including depression [ 103 , 104 , 105 ]. ADORA1 activation has been found to induce antidepressant-like effects [ 106 , 107 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic-Analysis-Oriented Drug Repurposing in the Search for Novel Antidepressants

Lesmana

Chiu

et al. 2022

Biomedicines

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From inadequate prior antidepressants that targeted monoamine neurotransmitter systems emerged the discovery of alternative drugs for depression. For instance, drugs targeted interleukin 6 receptor (IL6R) in inflammatory system. Genomic analysis-based drug repurposing using single nucleotide polymorphism (SNP) inclined a promising method for several diseases. However, none of the diseases was depression. Thus, we aimed to identify drug repurposing candidates for depression treatment by adopting a genomic-analysis-based approach. The 5885 SNPs obtained from the machine learning approach were annotated using HaploReg v4.1. Five sets of functional annotations were applied to determine the depression risk genes. The STRING database was used to expand the target genes and identify drug candidates from the DrugBank database. We validated the findings using the ClinicalTrial.gov and PubMed databases. Seven genes were observed to be strongly associated with depression (functional annotation score = 4). Interestingly, IL6R was auspicious as a target gene according to the validation outcome. We identified 20 drugs that were undergoing preclinical studies or clinical trials for depression. In addition, we identified sarilumab and satralizumab as drugs that exhibit strong potential for use in the treatment of depression. Our findings indicate that a genomic-analysis-based approach can facilitate the discovery of drugs that can be repurposed for treating depression.

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Sleeping Sickness Disrupts the Sleep-Regulating Adenosine System

Cited by 15 publications

References 67 publications

Many faces of sleep regulation: beyond the time of day and prior wake time

Many faces of sleep regulation: beyond the time of day and prior wake time

Distinct Differences in Gene Expression Profiles in Early and Late Stage Rhodesiense HAT Individuals in Malawi

Genomic-Analysis-Oriented Drug Repurposing in the Search for Novel Antidepressants

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