Transcriptome analysis of microglia in a mouse model of Rett syndrome: differential expression of genes associated with microglia/macrophage activation and cellular stress.
Dejian Zhao, Ryan Mokhtari, Erika Pedrosa and 3 others
PMID 28367307WHAT IT FOUND
Microglia from young female Rett-model mice showed gene changes before symptoms, including lower heat-shock genes.
In older symptomatic mice, changes were fewer and heat-shock genes were not different. This is a mouse brain-cell study, not a human treatment finding.
Key findings
01At 5 weeks, 464 genes differed; at 24 weeks, 79 genes differed.
02Heat-shock-related genes were significantly decreased in 5-week microglia but were not differentially expressed in 24-week microglia.
03Genes linked to M1 and M2 macrophage activation overlapped with the changed genes at both ages, but the direction of change did not match those activation states.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study was done in mice, not people, so it cannot show what would happen in a child with Rett syndrome. Only three Rett-model mice and three control mice were used at each age, for a total of 12 mice. The isolated microglia were not separated into cells with or without the Mecp2 gene, and the authors estimated that about 40% of the sequenced cells may have lacked it. The results describe gene expression, not a tested treatment, and they do not show that the changed genes cause symptoms. The overlap with macrophage activation genes did not match the direction of change, so it does not prove a simple inflammatory state. One 24-week sample showed more variation from the other two replicates.
Declared interests
The paper states funding from the National Institute of Mental Health and the National Institutes of Health. It does not report a commercial conflict of interest.
The easy way to misread this
Do not read this as evidence that a treatment changes microglia or symptoms in people with Rett syndrome. It measured gene expression in mouse brain cells and did not test therapy or clinical outcomes.