Omics · study · 2026
Botulinum Neurotoxin A Signaling in Pain Modulation within Human Sensory Neurons
Listed in NCBI GEO
Botulinum Neurotoxin A1 (BoNT/A1) is an effective treatment for chronic migraines, but its direct mechanism of action on human sensory neurons has not been tested.
Description
While rodent studies on dorsal root ganglion (DRG) and trigeminal ganglion (TG) show that BoNT/A1 inhibits neurotransmission, including calcitonin gene-related peptide (CGRP) release, by cleaving SNAP-25, only one previous study has assessed its effect on human DRG neurons .
The objective of this study was to understand the mechanism of action of BoNT/A1 in human sensory neurons and assess, using RNA sequencing, the transcriptomic consequences of BoNT/A1 treatment. Using DRGs obtained from organ donors the expression of key targets, including SNAP25, SV2C, & CALCA, was validated by mining existing transcriptomic datasets as well as immunohistochemistry. Cultured dissociated human DRG neurons treated with BoNT/A1 were used to examine cleavage of SNAP25, release of CGRP and transcriptomic changes after BoNT/A1 treatment.
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SV2C was found to be widely expressed in human DRG neurons in a pattern that completely overlapped with CGRP expression. Consistent with this finding, BoNT/A1 disrupted SNARE protein complexes in human DRG neurons as demonstrated by SNAP-25 cleavage in most somatosensory neurons and a reduction in capsaicin-evoked CGRP release, indicating impaired vesicle fusion. Moreover, Bulk RNA sequencing experiments revealed downregulated expression of a large subset of genes responsible for neurotransmitter and neuropeptide release from neurons suggesting a novel mechanism through which BoNT/A regulates neurotransmission.
These results provide new insight into the molecular mechanisms by which BoNT/A may exert its pain-relieving effects in humans.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300240 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300240 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1279966 ncbi.nlm.nih.gov/bioproject/PRJNA1279966 ↗
project · from NCBI GEO
- PubMed 40956003 pubmed.ncbi.nlm.nih.gov/40956003 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE300240 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |