A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase [brain regions]

An in-depth understanding of the molecular processes composing aging is crucial to develop therapeutic approaches that decrease aging as a key risk factor for cognitive decline. Herein, we present a spatio-temporal brain atlas (15 different regions) of microRNA expression across the mouse lifespan (7 time points) and two aging interventions. MicroRNAs are promising therapeutic targets, as they silence genes by complementary base-pair binding of messenger RNAs and mediate aging speed. We first established sex- and brain-region-specific microRNA expression patterns in young adult samples. Then we focused on sex-dependent and independent brain-region-specific microRNA expression changes during aging. We identified three sex-independent brain aging microRNAs (miR-146a-5p, miR-155-5p and miR-5100). For miR-155-5p, we showed that these expression changes are driven by aging microglia and target mTOR signaling pathway components and other cellular communication pathways. In this work, we identify strong sex-brain-region-specific aging microRNAs and microglial miR-155-5p as a promising therapeutic target. Overall design: From 75 C57BL/6JN mice (male and female), we obtain samples from fifteen different brain regions (three cortical regions (motor cortex, visual cortex and entorhinal cortex), anterior (dorsal) and posterior (ventral) hippocampus, hypothalamus, thalamus, caudate putamen (part of the striatum), pons, medulla, cerebellum and the olfactory bulb, corpus callosum, choroid plexus and the subventricular zone) and seven differnt age stages (3 month to 28 months). Analysing was done using the miRNA sequencing data.