Project description:To uncover abnormally regulated genes in OGT-KO SCs, we performed gene expression profiling experiments using sciatic nerves from 1-month-old OGT-SCKO and wildtype mice.
Project description:Sciatic nerve ligation was performed on cohorts of 2-month and 24-month old animals. Resulting gene-expression data were generated from sciatic nerve 1 and 4 days after injury compared to naïve animals. Results show differences in sciatic nerve responses with normal aging. Total RNA taken from sciatic nerves from 2-month and 24-month old animals at either day 0, 1 and 4 after sciatic nerve crush injury.
Project description:Gene expression analysis of 2-month-old Ctrl and Tfam-SCKO mice. At this age mitochondrial function is disrupted in the Schwann cells of Tfam-SCKO mice ,but their nerves display only very limited pathology. Mitochondrial dysfunction is a common cause of peripheral neuropathy. Much effort has been devoted to examining the role played by neuronal/axonal mitochondria, but how mitochondrial deficits in peripheral nerve glia (Schwann cells, SCs) contribute to peripheral nerve diseases remains unclear. Here, we investigate a mouse model of peripheral neuropathy secondary to SC mitochondrial dysfunction (Tfam-SCKOs). We show that disruption of SC mitochondria activates a maladaptive integrated stress response through actions of heme-regulated inhibitor kinase (HRI), and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. These alterations in SC lipid metabolism result in depletion of important myelin lipid components as well as in accumulation of acylcarnitines, an intermediate of fatty acid b-oxidation. Importantly, we show that acylcarnitines are released from SCs and induce axonal degeneration. A maladaptive integrated stress response as well as altered SC lipid metabolism are thus underlying pathological mechanisms in mitochondria-related peripheral neuropathies. Total RNA samples were prepared by isolating and pooling RNA from three different 2-month-old MPZ-Tfam KO and Ctrl mice. 2 replicates per genotype were used in this experiment and they were prepared entirely independently.
Project description:Transcriptomics and phosphoproteomics were carried out in B6.Cg-Mapttm1(EGFP)Klt (mapt knockout: tau-KO) and wild-type (WT) 12-month-old mice to learn about the effects of tau ablation.
Project description:Sciatic nerve ligation was performed on cohorts of 2-month and 24-month old animals. Resulting gene-expression data were generated from sciatic nerve 1 and 4 days after injury compared to naïve animals. Results show differences in sciatic nerve responses with normal aging.
Project description:The objective of this study was to determine which pathways are significantly regulated with age in sciatic and radial nerves, individually or considering the interaction term. We find a strong signature of the cholesterol biosynthesis pathway being downregulated with age in both nerves, however, this effect is significantly milder in the radial nerve. We collected both radial and sciatic nerves from 8 adult (8 months old) and 8 old (24 months old) rats.
Project description:In order to uncover the biological processes affected in glial cells by aging, we analyzed microarray gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time-points throughout life, from day of birth until senescence. In addition, we combined these data with the microarray gene expression data of myelin 56 day-old mouse mutants carrying deletions of either Pmp22, SCAP or Lpin1. Seven mice were dissected per developmental or aging time-point. Both sciatic nerves were isolated from each mouse and tissues were pooled per time-point to extract total RNA. For the mutants and their wild-type littermates, sciatic nerves were dissected from three mice per genotype. Tissues were not pooled, which generated triplicates per genotype. Total RNA was extracted, purified and quality-controlled. For each condition, 300 ng of total RNA was used to synthesize cRNA using the Illumina TotalPrep RNA amplification kit (Ambion). The cRNA was then quantified, quality controlled and hybridized to the MouseWG-6 v1 expression Beadchips (Illumina) according to the manufacturerM-^Rs instructions.
Project description:Ebf genes regulate differentiation of several cell type. Ebf2 is expressed in Schwann cells and Ebf2-/- mice show among other phenotypical abnormalities a delay in the onset of myelination associated to a decreased expression of genes regulating myelination. In addition at one month of age Ebf2-/- mice show decreased motor conduction velocity and morphological alteration in sciatic nerves. Ebf2 target genes are unknown. To identify Ebf2 target genes with a role in myelination, we compared the expression profiles of sciatic nerves isolated from P2 Wt and Ebf2-/- mice by microarray analysis. We used microarray to find Ebf2 candidate target genes by comparing gene expression of Ebf2-/- sciatic nerve and wt nerves 2 days postnatally (P2) a time point in which Ebf2-/- pups present a delay in the onset of myelination.
Project description:miRNAs are critical for myelination in the peripheral nervous system. We report the differential expression of miRNAs during myelination in sciatic nerves of wild-type mice. This data serves as a starting point to identify physiologically relevant regulatory miRNAs in the peripheral nervous system.
Project description:Our objective was to identify early changes in gene expression related to the development of sarcopenia via transcriptomic profiling of aging sciatic nerves in vivo. Sciatic nerve mRNA profiles of C57BL/6JN mice aged 5 (n = 6), 18 (n = 5), 21 (n = 6), and 24 months (n = 5) old were generated by RNA sequencing using an Illumina HiSeq4000. The sequence reads that passed quality filters were mapped to the mouse reference genome using STAR and featureCounts. Differential expression analysis was performed using DESeq2. Differentially expressed genes were validated using quantitative reverse transcription PCR (qRT-PCR) using SYBR Green assays. We detected 51 significant differentially expressed genes in sciatic nerve of 18-month-old mice compared to 5-month-old mice. These genes were associated with the AMPK signaling pathway, biosynthesis and metabolic pathways, and circadian rhythm. These early molecular changes shed a new light on biological processes in peripheral nerve that may be implicated in sarcopenia initiation and pathogenesis. Future studies are warranted to confirm the disease modifying and/or biomarker potential of the key changes we report here.