scholarly journals Physical Activity Induces Nucleus Accumbens Genes Expression Changes Preventing Chronic Pain Susceptibility Promoted by High-Fat Diet and Sedentary Behavior in Mice

2019 ◽  
Author(s):  
Arthur de Freitas Brandão ◽  
Ivan José Magayewski Bonet ◽  
Marco Pagliusi ◽  
Gabriel Gerardini Zanetti ◽  
Nam Pho ◽  
...  

AbstractHigh-fat diet (HFD)-induced obesity was reported to increase pain behavior independent of obesity status in rats, whereas weight loss interventions such as voluntary physical activity (PA) for adults with overweight or obesity was reported to promote pain reduction in humans with chronic pain (CP). However, is unknown whether an HFD and sedentary (SED) behavior is underlying to CP susceptibility and whether voluntary PA can prevent it. Moreover, differential gene expression in the nucleus accumbens (NAc) is considered to play a crucial role in CP susceptibility. The present study used an adapted model of the inflammatory prostaglandin E2 (PGE)-induced persistent hyperalgesia (PH-ST) protocol for mice, an HFD, and a voluntary PA paradigm to test these hypotheses. In addition, we performed a transcriptome in the NAc and a gene ontology enrichment tools to investigate the differential gene expression and identify the biological processes associated with CP susceptibility tested here. Our results demonstrated that HFD and sedentary behavior promoted CP susceptibility, which in turn was prevented by voluntary PA, even when the animals were fed an HFD. Transcriptome in the NAc found 2,204 differential expression genes related CP susceptibility promoted by HFD and sedentary behavior and prevented by voluntary PA. The gene ontology enrichment revealed 41 biological processes implicated in CP susceptibility. Analyzing collectively those biological processes, our results suggested that genes related to metabolic and mitochondria stress were up-regulated in the CP susceptibility group, whereas genes related to neuroplasticity and axonogenesis were up-regulated in the CP prevented group. These findings provide pieces of evidence that an HFD and sedentary behavior promoted gene expression changes in the NAc related to neurodegeneration and those changes were also underlying to CP susceptibility. Additionally, our findings confirmed other findings supporting the crucial role of voluntary PA to prevent CP susceptibility and add novel insights of differential gene expression in the NAc related to neuroplasticity.

2020 ◽  
Vol 13 ◽  
Author(s):  
Arthur Freitas Brandão ◽  
Ivan José Magayewski Bonet ◽  
Marco Pagliusi ◽  
Gabriel Gerardini Zanetti ◽  
Nam Pho ◽  
...  

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0213474 ◽  
Author(s):  
Tsering Stobdan ◽  
Debashis Sahoo ◽  
Priti Azad ◽  
Iain Hartley ◽  
Erilynn Heinrichsen ◽  
...  

2020 ◽  
Author(s):  
A. Louise Hunter ◽  
Charlotte E. Pelekanou ◽  
Nichola J. Barron ◽  
Rebecca C. Northeast ◽  
Antony Adamson ◽  
...  

ABSTRACTThe circadian clock component REVERBα is considered a dominant regulator of lipid metabolism, with global Reverbα deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (ReverbαFlox2-6AdipoCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of REVERBα regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, ReverbαFlox2-6AdipoCre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT REVERBα cistrome with differential gene expression reveals broad control of metabolic processes by REVERBα which is unmasked in the obese state. Adipocyte REVERBα does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, REVERBα action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.


2019 ◽  
Author(s):  
Pingtao Ding ◽  
Bruno Pok Man Ngou ◽  
Oliver J. Furzer ◽  
Toshiyuki Sakai ◽  
Ram Krishna Shrestha ◽  
...  

SUMMARYSequence capture followed by next-generation sequencing has broad applications in cost-effective exploration of biological processes at high resolution [1, 2]. Genome-wide RNA sequencing (RNA-seq) over a time course can reveal the dynamics of differential gene expression. However, in many cases, only a limited set of genes are of interest, and are repeatedly used as markers for certain biological processes. Sequence capture can help generate high-resolution quantitative datasets to assess changes in abundance of selected genes. We previously used sequence capture to accelerate Resistance gene cloning [1, 3, 4], investigate immune receptor gene diversity [5] and investigate pathogen diversity and evolution [6, 7].The plant immune system involves detection of pathogens via both cell-surface and intracellular receptors. Both receptor classes can induce transcriptional reprogramming that elevates disease resistance [8]. To assess differential gene expression during plant immunity, we developed and deployed quantitative sequence capture (CAP-I). We designed and synthesized biotinylated single-strand RNA bait libraries targeted to a subset of defense genes, and generated sequence capture data from 99 RNA-seq libraries. We built a data processing pipeline to quantify the RNA-CAP-I-seq data, and visualize differential gene expression. Sequence capture in combination with quantitative RNA-seq enabled cost-effective assessment of the expression profile of a specified subset of genes. Quantitative sequence capture is not limited to RNA-seq or any specific organism and can potentially be incorporated into automated platforms for high-throughput sequencing.


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 770 ◽  
Author(s):  
Santos ◽  
Icyuz ◽  
Pound ◽  
William ◽  
Guo ◽  
...  

Knowledge about synthetic lethality can be applied to enhance the efficacy of anticancer therapies in individual patients harboring genetic alterations in their cancer that specifically render it vulnerable. We investigated the potential for high-resolution phenomic analysis in yeast to predict such genetic vulnerabilities by systematic, comprehensive, and quantitative assessment of drug–gene interaction for gemcitabine and cytarabine, substrates of deoxycytidine kinase that have similar molecular structures yet distinct antitumor efficacy. Human deoxycytidine kinase (dCK) was conditionally expressed in the Saccharomyces cerevisiae genomic library of knockout and knockdown (YKO/KD) strains, to globally and quantitatively characterize differential drug–gene interaction for gemcitabine and cytarabine. Pathway enrichment analysis revealed that autophagy, histone modification, chromatin remodeling, and apoptosis-related processes influence gemcitabine specifically, while drug–gene interaction specific to cytarabine was less enriched in gene ontology. Processes having influence over both drugs were DNA repair and integrity checkpoints and vesicle transport and fusion. Non-gene ontology (GO)-enriched genes were also informative. Yeast phenomic and cancer cell line pharmacogenomics data were integrated to identify yeast–human homologs with correlated differential gene expression and drug efficacy, thus providing a unique resource to predict whether differential gene expression observed in cancer genetic profiles are causal in tumor-specific responses to cytotoxic agents.


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