Project description:Alterations in the composition of the gut microbiome have an emerging role in brain function and behaviour. We have porposed that short chain fatty acids (SCFA) including propionate and butyrate which are present in the diet and are fermantation products of many gastrointestinal bacteria are contributing environmental factors in autism spectrum disorders (ASD). Here we used the microarray technology to compare global changes in gene expression profiles following exposure of PC12 cells to structurally related SCFA propionate and butyrate each in two different concentrations. Large number of affected genes, common for both SCFA were identified, including genetic networks and GO processes implicated in ASD. PC12 cells were exposed to propionate or butyrate. RNA was isolated from each experimental group (n=6, pooled samples) and subjected to genome-wide expression profiling using Affymetrix microarrays to reveal dose- and SCFA-specific changes in gene expression and specific molecular pathways or processes affected as compared to vehicle treated controls.
Project description:Alterations in the composition of the gut microbiome have an emerging role in brain function and behaviour. We have porposed that short chain fatty acids (SCFA) including propionate and butyrate which are present in the diet and are fermantation products of many gastrointestinal bacteria are contributing environmental factors in autism spectrum disorders (ASD). Here we used the microarray technology to compare global changes in gene expression profiles following exposure of PC12 cells to structurally related SCFA propionate and butyrate each in two different concentrations. Large number of affected genes, common for both SCFA were identified, including genetic networks and GO processes implicated in ASD.
Project description:The role of post-transcriptional gene regulation in human brain development and cognitive diseases remains mostly uncharacterized. ELAV-like RNA binding proteins are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission. Here, we identify the downstream transcriptional networks of ELAVL2, an RNA-binding protein with unknown function in the brain. We knockdown expression of ELAVL2 in human neurons and conduct RNA-sequencing, identifying networks of differentially expressed and alternatively spliced genes with altered ELAVL2. These networks contain autism-relevant genes as well as previously identified targets of other RNA binding proteins implicated in autism spectrum disorders such as RBFOX1 and FMRP. ELAVL2-regulated coexpression networks are also enriched for synaptic genes as well as genes with human-specific patterns of gene expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal functions at risk in autism spectrum disorders and such mechanisms of post-transcriptional gene regulation may have contributed to human brain evolution.
Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes
