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Spatial transcriptomic alterations of the dorsal horn in dogs with neuropathic pain
Tenna Remler Pedersen1, Jørgen Steen Agerholm1, Clare Rusbridge2
1Department of Clinical Veterinary Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Introduction:
Microglia and astrocytes are believed to play a central role in the pathogenesis of neuropathic pain (NeP). These glial cells are commonly identified by the expression of ionized calcium-binding adaptor molecule 1 (IBA1) for microglia and glial fibrillary acidic protein (GFAP) for astrocytes. Under pathological conditions, astrocytes and microglia undergo both morphological and transcriptional changes, which may promote shifts in functions that can have both protective and detrimental effects on the surrounding neuroparenchyma. Like humans, the dog breed Cavalier King Charles Spaniels (CKCSs) suffers from heritable syringomyelia (SM) which in both species is associated with NeP.
Objectives:
To investigate the potential role of IBA1 and GFAP-positive cells in the dorsal horn in CKCSs with SM and NeP.
Methods:
Using NanoString GeoMx technology, we conducted spatial transcriptomic analyses on spinal cord dorsal horns from CKCSs with SM and NeP.
Results:
Several differentially expressed genes were identified in dogs with SM and NeP. Cells positive for IBA1 showed upregulation of inflammatory genes as well as a downregulation of immune functions, while GFAP-positive cells indicated different states of reactivity. Pathway analyses indicated that the PI3K-Akt signaling pathway may be involved in the generation of NeP in CKCSs with SM.
Conclusion:
These findings provide new insights into the complex molecular changes in dorsal horn IBA1 and GFAP-rich areas in the presence of NeP and SM. The findings of this study serve as a foundation for future research that may facilitate new understandings of NeP mechanisms.
Insights
Neuropathic pain (NeP) in Cavalier King Charles Spaniels with syringomyelia (SM) involves glial cell changes. Spatial transcriptomics revealed altered inflammatory and immune gene expression in microglia (IBA1) and astrocytes (GFAP).
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia (ionized calcium-binding adaptor molecule 1, IBA1) and astrocytes (glial fibrillary acidic protein, GFAP) are implicated in neuropathic pain (NeP).
- Cavalier King Charles Spaniels (CKCSs) with heritable syringomyelia (SM) experience NeP, mirroring human conditions.
- Glial cells undergo significant morphological and transcriptional alterations in pathological states, influencing neural function.
Purpose of the Study:
- To investigate the role of IBA1-positive microglia and GFAP-positive astrocytes in the dorsal horn of CKCSs with SM and NeP.
- To identify molecular changes associated with NeP in this canine model.
Main Methods:
- Spatial transcriptomic analysis using NanoString GeoMx technology.
- Examination of spinal cord dorsal horns from CKCSs affected by SM and NeP.
Main Results:
- Identification of differentially expressed genes in dogs with SM and NeP.
- Upregulation of inflammatory genes and downregulation of immune functions in IBA1-positive cells.
- Distinct reactivity states observed in GFAP-positive astrocytes.
- The PI3K-Akt signaling pathway implicated in NeP generation.
Conclusions:
- Provides novel insights into molecular alterations in glial-rich dorsal horn areas during NeP in CKCSs with SM.
- Establishes a foundation for future research into NeP mechanisms.
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