ArticleFrontiers in molecular neuroscience2022
Sexually dimorphic transcriptional programs of early-phase response in regenerating peripheral nerves.
Article in Frontiers in molecular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Deletion of Pax1 scoliosis-associated regulatory elements leads to a female-biased tail abnormality.Cell reports · 2024Article
- Communicating pain: emerging axonal signaling in peripheral neuropathic pain.Frontiers in neuroanatomy · 2024Review
- Application of Electrical Stimulation to Enhance Axon Regeneration Following Peripheral Nerve Injury.Bio-protocol · 2023Article
- Sexual dimorphism of early transcriptional reprogramming in degenerating peripheral nerves.Frontiers in molecular neuroscience · 2022Article
- Sex differences in Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy and experimental autoimmune neuritis.Frontiers in immunology · 2022Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
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Abstract
The convergence of transcriptional and epigenetic changes in the peripheral nervous system (PNS) reshapes the spatiotemporal gene expression landscape in response to nerve transection. The control of these molecular programs exhibits sexually dimorphic characteristics that remain not sufficiently characterized. In the present study, we recorded genome-wide and sex-dependent early-phase transcriptional changes in regenerating (proximal) sciatic nerve 24 h after axotomy. Male nerves exhibited more extensive transcriptional changes with male-dominant upregulation of cytoskeletal binding and structural protein genes. Regulation of mRNAs encoding ion and ionotropic neurotransmitter channels displayed prominent sexual dimorphism consistent with sex-specific mRNA axonal transport in an early-phase regenerative response. Protein kinases and axonal transport genes showed sexually dimorphic regulation. Genes encoding components of synaptic vesicles were at high baseline expression in females and showed post-injury induction selectively in males. Predictive bioinformatic analyses established patterns of sexually dimorphic regulation of neurotrophic and immune genes, including activation of glial cell line-derived neurotrophic factor Gfra1 receptor and immune checkpoint cyclin D1 (Ccnd1) potentially linked to X-chromosome encoded tissue inhibitor of matrix metallo proteinases 1 (Timp1). Regulatory networks involving Olig1, Pou3f3/Oct6, Myrf, and Myt1l transcription factors were linked to sex-dependent reprogramming in regenerating nerves. Differential expression patterns of non-coding RNAs motivate a model of sexually dimorphic nerve regenerative responses to injury determined by epigenetic factors. Combined with our findings in the corresponding dorsal root ganglia (DRG), unique early-phase sex-specific molecular triggers could enrich the mechanistic understanding of peripheral neuropathies.
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