Neurotoxicity is a common side effect of chemotherapeutics that often leads to the development of chemotherapy-induced peripheral neuropathy (CIPN). The peptide Prokineticin 2 (PK2) has a key role in experimental models of CIPN and can be considered an insult-inducible endangering mediator. Since primary afferent sensory neurons are highly sensitive to anticancer drugs, giving rise to dysesthesias, the aim of our study was to evaluate the alterations induced by vincristine (VCR) and bortezomib (BTZ) exposure in sensory neuron cultures and the possible preventive effect of blocking PK2 signaling. Both VCR and BTZ induced a concentration-dependent reduction of total neurite length that was prevented by the PK receptor antagonist PC1. Antagonizing the PK system also reduced the upregulation of PK2, PK-R1, TLR4, IL-6, and IL-10 expression induced by chemotherapeutic drugs. In conclusion, inhibition of PK signaling with PC1 prevented the neurotoxic effects of chemotherapeutics, suggesting a promising strategy for neuroprotective therapies against the sensory neuron damage induced by exposure to these drugs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541916 | PMC |
| http://dx.doi.org/10.3389/fimmu.2020.02119 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Defects in hair cells disrupt the development of auditory peripheral circuitry.
Nat Commun
December 2024
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Deafness is the most common form of sensory impairment in humans and frequently caused by defects in hair cells of the inner ear. Here we demonstrate that in male mice which model recessive non-syndromic deafness (DFNB6), inactivation of Tmie in hair cells disrupts gene expression in the neurons that innervate them. This includes genes regulating axonal pathfinding and synaptogenesis, two processes that are disrupted in the inner ear of the mutant mice.
View Article and Find Full Text PDFMolecular characterization of the sea lamprey retina illuminates the evolutionary origin of retinal cell types.
Nat Commun
December 2024
Department of Ophthalmology and Stein Eye Institute, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
The lamprey, a primitive jawless vertebrate whose ancestors diverged from all other vertebrates over 500 million years ago, offers a unique window into the ancient formation of the retina. Using single-cell RNA-sequencing, we characterize retinal cell types in the lamprey and compare them to those in mouse, chicken, and zebrafish. We find six cell classes and 74 distinct cell types, many shared with other vertebrate species.
View Article and Find Full Text PDFDLK-dependent axonal mitochondrial fission drives degeneration after axotomy.
Nat Commun
December 2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.
View Article and Find Full Text PDFAutologous Fascia Nerve Wrap in a Rodent Primary Epineurial Repair Model and Preliminary Case Series.
Plast Reconstr Surg
December 2024
Department of Plastic and Reconstructive Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Background: Nerve wraps composed of various autologous and bioengineered materials have been used to bolster nerve repair sites. In this study, we describe the novel use of autologous fascia nerve wraps (AFNW) as an adjunct to epineurial repair and evaluate their effect on inflammatory cytokine expression, intraneural collagen deposition and end-organ reinnervation in rats and use of AFNW in a patient case series.
Methods: Lewis rats received sciatic transection with repair either with or without AFNW, sciatic-to-common peroneal nerve transfer with or without AFNW, or sham surgery (n=14/group).
Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons.
J Transl Med
December 2024
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Taltirelin, an orally effective thyrotropin-releasing hormone analog, significantly improves motor impairments in rat models of Parkinson's disease (PD) and enhances dopamine release within the striatum. However, the underlying mechanism remains unclear. In this study, a variety of in vivo and in vitro methods, including transcriptomic analysis, were employed to elucidate the effects of Taltirelin on cellular composition and signaling pathways in the striatum of hemi-PD rats.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!