Dataset Information

GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome.

ABSTRACT: Wolfram syndrome (WS) is a rare neurodegenerative disorder that is mainly characterized by diabetes mellitus, optic nerve atrophy, deafness, and progressive brainstem degeneration. Treatment with GLP-1 receptor agonists has shown a promising anti-diabetic effect in WS treatment in both animal models and in human patients. Since previous research has tended to focus on investigation of the WS first symptom, diabetes mellitus, the aim of the present study was to examine liraglutide effect on WS-associated neurodegeneration. We took 9-month-old Wfs1 knock-out (KO) animals that already had developed glucose intolerance and treated them with liraglutide for 6 months. Our research results indicate that 6-month liraglutide treatment reduced neuroinflammation and ameliorated endoplasmic reticulum (ER) stress in the inferior olive of the aged WS rat model. Liraglutide treatment also protected retinal ganglion cells from cell death and optic nerve axons from degeneration. According to this, the results of the present study provide novel insight that GLP-1 receptor agonist liraglutide has a neuroprotective effect in the WS rat model.

SUBMITTER: Seppa K

PROVIDER: S-EPMC6823542 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome.

Seppa Kadri K Toots Maarja M Reimets Riin R Jagomäe Toomas T Koppel Tuuliki T Pallase Maia M Hasselholt Stine S Krogsbæk Mikkelsen Maiken M Randel Nyengaard Jens J Vasar Eero E Terasmaa Anton A Plaas Mario M

Scientific reports 20191031 1

Wolfram syndrome (WS) is a rare neurodegenerative disorder that is mainly characterized by diabetes mellitus, optic nerve atrophy, deafness, and progressive brainstem degeneration. Treatment with GLP-1 receptor agonists has shown a promising anti-diabetic effect in WS treatment in both animal models and in human patients. Since previous research has tended to focus on investigation of the WS first symptom, diabetes mellitus, the aim of the present study was to examine liraglutide effect on WS-as ...[more]

PMID: 31673100

Similar Datasets

Project description:B6.Cg-Lep ob/ob mice females were surgically implanted in an age of 10-12 weeks with Alzet osmotic mini pumps (model 1002, 0,25l/h, Cupertino, CA, USA) in two groups of ten mice each to perform continuous subcutaneous infusions of Dulbecco's phosphate buffered saline (vehicle; n = 8) or GLP-1 (GLP-1; n = 9) agonist Liraglutide (Victoza, batch# CS6C214, Novo Nordisk A/S, Bagsvaerd, Denmark) to investigate the effects of the respective treatment on peri-gonadal epididymal white adipose tissue gene expression. Vehicle or Liraglutide at a dose of 600 g/kg/d were continuously infused (at a dose of 600 g/kg/d) over a 14 days period. On the morning after the osmotic mini pump reservoirs liquid content should have been consumed mice were dissected to remove the peri-gonadal epididymal fat pad for white adipose tissue gene expression analysis. At least 220 mg of white adipose tissue was quickly removed, shock-frozen in liquid nitrogen and thereafter stored at -80C for mRNA extraction. To perform RNA-Seq analysis, samples were single-end sequenced at a depth of 75 80M reads per sample with a read-length of 51 bp using an Illumina Hiseq2500. Raw sequencing files were quality controlled with FastQC. Alignment and trimming of reads was performed using the OSA algorithm against the mouse reference genome b38.1 with RefSeq as the gene model as implemented in OmicSoft ArraySuite software, version 8. RNA transcripts were quantified using RSEM methods as implemented in Arraystudio counting count the read fragments mapping to each individual gene and quantify expression by the corresponding FPKM. In summary, expression was measured as FPKM for 25,054 unique genes. Principal component analysis was then performed to check for possible batch effects and outliers complemented by calculating the RNA-Seq 5'->3' trend for each sample. One sample for the vehicle control as well as for the Liraglutide group were identified as outliers and removed from subsequent analysis, resulting in 7 and 8 samples remaining for each group respectively. Abundance values (counts) were normalized and compared between liraglutide treated mice versus baseline controls using DESeq2. All P-values were adjusted for multiple testing by the Benjamini-Hochberg method.

Dataset Information

GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome.

Publications

GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets