1. Analgesic targets identified in mouse sensory neuron somata and terminal pain translatomes.
- Author
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Bangash MA, Cubuk C, Iseppon F, Haroun R, Garcia C, Luiz AP, Arcangeletti M, Gossage SJ, Santana-Varela S, Cox JJ, Lewis MJ, Wood JN, and Zhao J
- Subjects
- Animals, Mice, Male, Female, Protein Biosynthesis, NAV1.7 Voltage-Gated Sodium Channel metabolism, NAV1.7 Voltage-Gated Sodium Channel genetics, Glutamate Decarboxylase metabolism, Glutamate Decarboxylase genetics, Polyribosomes metabolism, Mice, Inbred C57BL, Ganglia, Spinal metabolism, Sensory Receptor Cells metabolism, Pain metabolism
- Abstract
The relationship between transcription and protein expression is complex. We identified polysome-associated RNA transcripts in the somata and central terminals of mouse sensory neurons in control, painful (plus nerve growth factor), and pain-free conditions (Nav1.7-null mice). The majority (98%) of translated transcripts are shared between male and female mice in both the somata and terminals. Some transcripts are highly enriched in the somata or terminals. Changes in the translatome in painful and pain-free conditions include novel and known regulators of pain pathways. Antisense knockdown of selected somatic and terminal polysome-associated transcripts that correlate with pain states diminished pain behavior. Terminal-enriched transcripts included those encoding synaptic proteins (e.g., synaptotagmin), non-coding RNAs, transcription factors (e.g., Znf431), proteins associated with transsynaptic trafficking (HoxC9), GABA-generating enzymes (Gad1 and Gad2), and neuropeptides (Penk). Thus, central terminal translation may well be a significant regulatory locus for peripheral input from sensory neurons., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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