Axon Transcriptomics
Analysis of changes in axonal mRNA transcriptomes in embryonic and adult DRG primary neurons during neuronal sensitisation after PGE2
Versus Arthritis Pain Centre Labs
Investigators
- Asta Tranholm
- Rafael Fort
- Rebecca Pope
The nociceptor neurons found in the dorsal root ganglia (DRG) transmit pain signals from the periphery to the spinal cord, through their very long axons. Chronic pain states can occur when these neurons become hypersensitive to pain signals, in a process that requires neuronal plasticity. One of the mediators of primary hyperalgesia is prostaglandin E2 (PGE2), which is elevated in pain conditions such as osteoarthritis. In other types of neurons, plasticity is often mediated by the regulated translation of mRNAs localised to the neurites, including the axon. In this study, we investigated the subcellular localisation of mRNAs to the axons of DRG neurons from both embryonic (E16.5) and adult mice and examined the effect of PGE2 on mRNA localisation and calcium signalling. We used compartmentalised modified Boyden chambers to extract RNA from subcellular domains (axons v cell bodies/soma) and identify changes in mRNA transcriptomics. Our bioinformatics analysis has allowed us to define key transcripts that are significantly increased in the axon compartment of embryonic and adult neurons, and to develop localised knockdown approaches to prevent neuronal sensitisation driven by PGE2 stimulation (manuscript in preparation).
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