ArticleInternational journal of molecular sciences2022
PACAP-38 Induces Transcriptomic Changes in Rat Trigeminal Ganglion Cells Related to Neuroinflammation and Altered Mitochondrial Function Presumably via PAC1/VPAC2 Receptor-Independent Mechanism.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Adcyap1r1-driven astrocyte reprogramming attenuates neuroinflammation and promotes dopaminergic neuroprotection in Parkinson's Disease.Stem cell research & therapy · 2026Article
- PACAP Alleviates Paclitaxel-Induced Peripheral Neuropathy by Targeting Oxidative Stress and Mitochondrial Damage via the PGC-1α Pathway.CNS neuroscience & therapeutics · 2026Article
- Possible Role of Novel Mitochondrial Subsets in Migraine.Life (Basel, Switzerland) · 2025Review
- Nuclear paraspeckle assembly transcript 1 promotes photophobia behavior in mice via miR-196a-5p/Trpm3 coupling.The journal of headache and pain · 2025Article
- PACAP38/mast-cell-specific receptor axis mediates repetitive stress-induced headache in mice.The journal of headache and pain · 2024Article
- Method for cryopreservation of trigeminal ganglion for establishing primary cultures of neurons and glia.Journal of neuroscience methods · 2024Article
- From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment.Cells · 2023Review
- Molecular Links between Sensory Nerves, Inflammation, and Pain 2.0.International journal of molecular sciences · 2023Article
- Energy metabolism disturbance in migraine: From a mitochondrial point of view.Frontiers in physiology · 2023Review
- Hemokinin-1 induces transcriptomic alterations in pain-related signaling processes in rat primary sensory neurons independent of NK1 tachykinin receptor activation.Frontiers in molecular neuroscience · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a broadly expressed neuropeptide which has diverse effects in both the peripheral and central nervous systems. While its neuroprotective effects have been shown in a variety of disease models, both animal and human data support the role of PACAP in migraine generation. Both PACAP and its truncated derivative PACAP(6-38) increased calcium influx in rat trigeminal ganglia (TG) primary sensory neurons in most experimental settings. PACAP(6-38), however, has been described as an antagonist for PACAP type I (known as PAC1), and Vasoactive Intestinal Polypeptide Receptor 2 (also known as VPAC2) receptors. Here, we aimed to compare the signaling pathways induced by the two peptides using transcriptomic analysis. Rat trigeminal ganglion cell cultures were incubated with 1 µM PACAP-38 or PACAP(6-38). Six hours later RNA was isolated, next-generation RNA sequencing was performed and transcriptomic changes were analyzed to identify differentially expressed genes. Functional analysis was performed for gene annotation using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome databases. We found 200 common differentially expressed (DE) genes for these two neuropeptides. Both PACAP-38 and PACAP(6-38) treatments caused significant downregulation of NADH: ubiquinone oxidoreductase subunit B6 and upregulation of transient receptor potential cation channel, subfamily M, member 8. The common signaling pathways induced by both peptides indicate that they act on the same target, suggesting that PACAP activates trigeminal primary sensory neurons via a mechanism independent of the identified and cloned PAC1/VPAC2 receptor, either via another target structure or a different splice variant of PAC1/VPAC2 receptors. Identification of the target could help to understand key mechanisms of migraine.
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Registered trials
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