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Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin-A (BoNT-A)

ABSTRACT: Introduction:The purpose of this study is to provide athe first global transcriptomic profiling and systems analysis of BoNT-A treated muscle over a one year period. Microarray analysis was performed on rat TA muscle from 4 groups (n=4/group) at 1,4, 12 and 52 weeks after BoNT-A injection and saline injected rats at 12 weeks as control. Fold changes were computed at each time point with respect to control. Results: Dramatic transcriptional adaptation occurs at 1 week with a paradoxical increase in expression of slow and immature isoforms; increased expression of genes in competing pathways of repair and atrophy; impaired mitochondrial biogenesis and increased metal ion imbalance. ECM adaptations occurred at 4weeks to the basal lamina and fibrillar ECM. The muscle transcriptome returned to the unperturbed state 12 weeks post-injection. Conclusion: Transcriptional adaptations resemble denervated muscle albeit some differences. Overall gene expression, across time, correlates with the generally accepted BoNT-A time course. Samples of Tibialis anterior (TA) muscle from 4 groups (n=4/group) of rats sacrificed at 1, 4, 12, and 52 weeks after BoNT-A injection, subject to affymetrix microarray analysis. In addition, contralateral TA from saline injected rats extracted at 12 weeks after saline injection was used as control tissue for the microarray analysis.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Kavitha Mukund

PROVIDER: E-GEOD-52350 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin-A (BoNT-A)

Project description:Introduction:The purpose of this study is to provide athe first global transcriptomic profiling and systems analysis of BoNT-A treated muscle over a one year period. Microarray analysis was performed on rat TA muscle from 4 groups (n=4/group) at 1,4, 12 and 52 weeks after BoNT-A injection and saline injected rats at 12 weeks as control. Fold changes were computed at each time point with respect to control. Results: Dramatic transcriptional adaptation occurs at 1 week with a paradoxical increase in expression of slow and immature isoforms; increased expression of genes in competing pathways of repair and atrophy; impaired mitochondrial biogenesis and increased metal ion imbalance. ECM adaptations occurred at 4weeks to the basal lamina and fibrillar ECM. The muscle transcriptome returned to the unperturbed state 12 weeks post-injection. Conclusion: Transcriptional adaptations resemble denervated muscle albeit some differences. Overall gene expression, across time, correlates with the generally accepted BoNT-A time course.

2014-11-01 | GSE52350 | GEO

Teriparatide changes the gene expression of dorsal root ganglia in ovariectomized rats

Project description:Twelve-week-old rats underwent bilateral ovariectomy (OVX) or sham surgery. Four weeks after surgery, the animals underwent the following treatments for 4 weeks: subcutaneous injection of teriparatide (TPTD) or saline 3 times weekly. All rats were anesthetized and sacrificed at the end of the experimental period. The L4-5 dorsal root ganglia (DRG) were harvested.

2020-03-30 | GSE121109 | GEO

Expression analysis in hipsc-derived neurons exposed to botulinum neurotoxin A subtype 1 and a type A atoxic derivative

Project description:Transcriptome analysis of RNA extracted from human induced pluripotent stem cell (hipsc)-derived neurons exposed to botulinum neurotoxin type A1 (BoNT/A1) and an atoxic derivative, BoNT/A ad. Botulinum neurotoxin type A1 (BoNT/A1) is a potent protein toxin responsible for the potentially fatal human illness botulism. Despite this, the long-lasting flaccid muscle paralysis caused by BoNT/A has led to its rise as a powerful and versatile bio-pharmaceutical. The flaccid paralysis is due to specific cleavage of SNAREs by BoNTs inside neurons. However, potential effects of BoNTs on intoxicated neurons besides the cleavage of SNAREs have not been studied in detail. In this study we investigated by microarray analysis the effects of BoNT/A and a catalytically inactive derivative (BoNT/A ad) on the transcriptome of human induced pluripotent stem cell (hiPSC)-derived neurons at 2 days and 2 weeks after exposure. While there were only minor changes in expression levels at 2 days post exposure, at 2 weeks post exposure 492 genes were differentially expressed more than 2-fold in BoNT/A1-exposed cells when compared to non-exposed populations, and 682 genes were differentially expressed in BoNT/A ad-exposed cells. The vast majority of genes were similarly regulated in BoNT/A1 and BoNT/A ad-exposed neurons, and the few genes differentially regulated between BoNT/A1 and BoNT/A ad-exposed neurons were regulated less than 3.5 fold. These data indicate a similar response of neurons to BoNT/A1 and BoNT/A ad exposure. The most highly regulated genes in cells exposed to either BoNT/A1 or BoNT/A ad are involved in neurite outgrowth and calcium channel sensitization.

2014-09-15 | GSE58149 | GEO

Variation of mRNA and lncRNA expression after using AMD3100 in rat chronic allograft nephropathy model.

Project description:To investigate the variation of mRNA and lncRNA expression after using AMD3100 in rat chronic allograft nephropathy model (CAN) model, we have employed mRNA and lncRNA microarray expression profiling as a discovery platform to identify genes with the potential. CAN rat models were established using male Fisher 344 to Lewis rats. Rats in the experimental group(n=3) were treated with AMD3100 (1 mg/kg/day subcutaneously, 0–12 weeks), rats in the control group(n=3) were treated with saline. The kidney grafts were harvested 12 weeks after modeling for microarray analysis.

2018-05-08 | GSE114088 | GEO

Neonatal Hydrocephalus: Saline Control vs. Kaolin-Induced

Project description:Transcriptional profiling of the parietal cortex was performed in postnatal day 22 rats with obstructive hydrocephalus. An intracisternal injection of kaolin was done on postnatal day one, and severe hydrocephalus developed over 3 weeks. Hydrocephalic animals were compared to age-matched saline controls. The goal was to determine the effects of kaolin-induced neonatal hydrocephalus on gene expression.

2010-07-01 | GSE16985 | GEO

Azoxymethane-induced colorectal tumorigenesis in hypertensive rat models

Project description:To compare the tumor susceptibility between the hypertensive Dahl salt-sensitive rats (S) rat and S.LEW(10)x12x2x3x5 (S.LEW) congenic strain, one of the S.LEW congenic strains our laboratory previously constructed on rat chromosome 10 [Hypertension. 2007 Nov;50(5):891-8], Azoxymethane (AOM)-induced colon tumorigenesis in rats was assessed. At six weeks of age, both S and S.LEW congenic rats received intraperitoneal (IP) injection of AOM in sterial saline at a dose of 15mg/kg body weight once a week for two consecutive weeks. At 30 weeks of age, all the rats were euthanized through carbon dioxide inhalation. The colon tissue was harvested, dissected longitudinally, and washed with saline. The number and size of the colon tumors were recorded. We found that the total number of colon tumors was significantly higher in the S.LEW congenic strain compared with the S rat. To further study the genetic and molecular mechanisms causing the higher tumor susceptibility in the S.LEW congenic strain, we have employed the whole genome microarray expression profiling to identify genes and signaling pathways that are differential between the S and S.LEW congenic strain. At six weeks of age, both S and S.LEW congenic rats received intraperitoneal (IP) injection of AOM in serial saline at a dose of 15mg/kg body weight once a week for two consecutive weeks. At 30 weeks of age, all the rats were euthanized through carbon dioxide inhalation. The colon tissue was harvested, dissected longitudinally, and washed with saline. RNA from the harvested colons of 3 S and 3 S.LEW congenic rats were prepared for the microarray study.

2016-04-04 | E-GEOD-75280 | biostudies-arrayexpress

Transcriptome analysis of dorsal root ganglion in rats with knee rheumatoid arthritis

Project description:To determine the LncRNA expression profile in dorsal root ganglia tissues of 7 days after rats received 150 μl of CFA (1 mg/ml Mycobacterium tuberculosis, Sigma, USA) through the patella tendon into the right knee joint. CFA injection rats macthed saline injection rats, we uesed LncRNA microArray analysis form Arraystar to examine the expression of LncRNAs and mRNAs in dorsal root ganglia tissues of 7 days after rats received CFA through the patella tendon into the right knee joint and matched Saline through the patella tendon into the right knee joint.

2020-11-12 | GSE146881 | GEO

Diaphragm in Diabetes

Project description:8 week old rats injected with streptozotocin or buffer alone at age of 8 weeks, diaphragm muscle obtained at age of 12 weeks (thus animals were diabetic for 4 weeks) Keywords: Disease state analysis (diabetes)

2009-11-13 | GSE4653 | GEO

Role of the Cytoskeleton in muscle transcriptional response to altered use

Project description:Desmin is a cytoskeletal protein in muscle involved in integrating cellular space and transmitting forces. In this study we sought to determine the combinatory effects of desmin deletion, aging and eccentric exercise on skeletal muscle at the transcriptional level across many pathways of muscle physiology. RNA was isolated from the TA muscle of mice of two genotypes (wildtype (WT) and desmin knockout (KO)) and two ages (7-9 weeks (Adult) and 12-14 months (Aged)). TA muscles were subjected to a bout of 50 eccentric contractions 12 hours prior to RNA isolation. Numbers per group are as follows: WT_Adult (5), WT_Aged (5), KO_Adult (5), KO_Aged (4).

2012-10-06 | E-GEOD-41363 | biostudies-arrayexpress

Gene expression profiling of sciatic nerves from rats with diabetic peripheral neuropathy

Project description:To identify the key genes and pathways which might play critical roles in the pathogenesis of experimental DPN via microarray analysis. Adult male Sprague-Dawley rats (initial weight 250-300g, from the department of laboratory animal science of Fudan University) were randomly assigned into two groups: control rats and diabetic rats. Diabetes was induced with a single intraperitoneal injection of STZ (55mg/kg). Control rats were performed with a single intraperitoneal injection of 0.9% saline solution. Glucose level was evaluated using Sannuo strips on tail vein blood at day 3 after STZ injection and verified again at day 7 after STZ injection. Only rats with blood glucose level 16.7 mmol/L were considered diabetic.Six weeks after diabetes induction, nerve tissue samples (about 1cm long) were harvested from the right sciatic nerve of rats in control (n=3) and diabetic (n=3) groups for total RAN isolation. Microarray hybridization was then performed according to the Agilent One-Color Microarray-Based Gene Expression Analysis protocol (Agilent Technologies). Quantile normalization and subsequent data processing were performed using the GeneSpring GX v12.1 software package (Agilent Technologies). The univariate t-test with a fold-change >2 and P value < 0.001 was applied to identify the DEGs between control rats and diabetic rats. Credibility of the microarray data was validated through qRT-PCR on 4 genes. Total RNA was independently extracted from the right sciatic nerve of rats in both groups (n=3) 6 weeks after diabetes induction.

2020-03-31 | GSE147732 | GEO

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