Journal: bioRxiv

Article Title: Glioma-Induced Alterations in Excitatory Neurons are Reversed by mTOR Inhibition

doi: 10.1101/2024.01.10.575092

Figure Lengend Snippet: a) Left: Coronal section of a mouse model of infiltrative glioma model showing an intermingling of mCherry+ glioma cells (red) with RiboTag (HA+; green) neurons. NeuN (magenta) is used to identify all neurons. Bar, 1mm. Right: Enlarged field from the cortex, showing prominent perineuronal satellitosis. Bar, 50 μm. b) GSEA plot showing enrichment of neuronal genes in the immunoprecipitated (IP) fraction of glioma-infiltrated brain. N = 3 mice per condition. c) Oral administration of AZD8055 effectively inhibits mTOR signaling in HA+ neurons in glioma-bearing mice. Representative images of cortex from mice treated with vehicle (top) or AZD8055 (bottom). Bar: 100 μm. Right: graph showing fluorescence intensity of pS6 (Ser240/244) levels in HA+ neurons, p=0.0004. N = 3 mice per condition, 15 image fields per condition. Wilcoxon rank-sum test was used. Yellow lines represent the mean. d) Map showing differential expression of neuronal-enriched genes between control brain, tumor brain, and tumor brain treated with AZD8055. N = 3 mice per condition. e) Gene ontologies that are altered between control and tumor brain and reversed by mTOR inhibition. N = 3 mice per condition. f) GSEA demonstrates depletion of inhibitory synapse genes in tumor brain compared to control (left) and an enrichment following AZD8055 treatment (right). N = 3 mice per condition. g) GSEA demonstrates enrichment of spine genes found in RNA granules in tumor brain compared to control (left) and their depletion following AZD8055 treatment (right). N = 3 mice per condition.

Article Snippet: All analyses were performed in pre-ranked mode using weighted statistics on the desktop GSEA software (version 4.3.2) downloaded from the Broad institute.

Techniques: Immunoprecipitation, Fluorescence, Quantitative Proteomics, Control, Inhibition