Journal: Brain
Article Title: Modelling fragile X-associated neuropsychiatric disorders in young inducible 90CGG premutation mice
doi: 10.1093/brain/awaf203
Figure Lengend Snippet: Activation of the 90CGG transgene induces time-dependent alterations in the ventral hippocampal (vH) proteome. ( A ) Mass spectrometry shows that transgene activation in adolescent (DOX+.7w) and young adult (DOX+.12w) mice alters the vH proteome. The volcano plot illustrates the log 2 fold change in protein expression versus the −log 10 of the false discovery rate for upregulated (red) and downregulated (blue) proteins with a false discovery rate > 0.05, comparing DOX−.7w ( n = 4) with DOX+.7w ( n = 3) and DOX−.12w ( n = 4) with DOX+.12w ( n = 3). ( B ) A heat map displays the top 50 enriched proteins in the data set, identified through gene set enrichment analysis (GSEA) for each experimental group. The colour gradient represents expression levels, ranging from lowest (blue) to highest (red). The data were normalized row-wise using z -score normalization. ( C ) Downregulated (blue) and upregulated (red) pathways in the vH proteome of adolescent mice (DOX+.7w) and young adult mice (DOX+.12w). Bars represent the normalized enrichment score with false discovery rate > 25% and a q -value > 0.05, based on the gene ontology (GO) biological process database. In adolescent mice, pathways related to cellular respiration, metabolism and immune response were enriched. In young adult mice, pathways related to cellular/aerobic respiration, oxidative stress and amino acid transport were upregulated, whereas pathways linked to the cytoskeletal organization (e.g. intermediate filament, actin cytoskeleton) and ionotropic glutamatergic signalling were downregulated. ( D ) Although adolescent and young adult mice with premutation show mainly diverging proteomic changes in the vH, several proteins with similar alterations are identified. Only two proteins (GABRA2 and HCN4) show opposite trends in their expression. Venn diagram (blue = decreased expression; red = increased expression) is based on data shown in B . Comparison of this dataset with previously published work revealed several proteins (highlighted in black) that had been identified in the intranuclear inclusions of FXTAS patients (marked with an asterisk), , , differentially expressed proteins in the synaptosome of the CGG KI mouse model (marked with two asterisks) and differentially expressed proteins in the CSF of FXTAS patients (marked with three asterisks). DOX = doxycycline; FDR = false discovery rate; FXTAS = fragile X-associated tremor/ataxia syndrome.
Article Snippet: Conversely, cytoskeletal organization (e.g. actin filament organization, postsynaptic actin cytoskeleton organization, actin filament depolymerization, intermediate filament organization) and glutamate receptor signalling (ionotropic glutamate receptor signalling pathway) were downregulated.
Techniques: Activation Assay, Mass Spectrometry, Expressing, Comparison
