Motoneuron activity is modulated by histamine receptors. While H1 and H2 receptors have been widely explored, H3 histamine receptors (H3Rs) have not been sufficiently characterized. This paper targets the effects of the selective activation of H3Rs and their expression on the membranes of large ventral horn cells. The application of selective pharmacological agents to spinal cords isolated from neonatal rats was used to identify the presence of functional H3Rs on the membrane of physiologically identified lumbar motoneurons. Intra and extracellular recordings revealed that H3R agonist, α-methylhistamine, depolarized both single motoneurons and ventral roots, even in the presence of tetrodotoxin, an effect prevented by H3R antagonist, thioperamide. Finally, immunohistochemistry located the expression of H3Rs on a subpopulation of large cells in lamina IX. This study identifies H3Rs as a new exploitable pharmacological target against motor disturbances.
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Dorsal root ganglion
H3 histamine receptors
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We thank Ms. Elvita Titolo and Mr Walter Zangrando for their generous support. We are grateful to Elisa Ius for the excellent assistance in preparing the manuscript.
Conflict of interest
The authors declare that they have no conflicts of interest.
Procedures were approved by the International School for Advanced Studies (SISSA) ethics committee and are in accordance with the guidelines of the Italian Animal Welfare Act 24/3/2014 n. 26 implementing the European Union directive on animal experimentation (2010/63/EU). All procedures performed in studies involving animals were in accordance with the ethical standards of the SISSA Laboratory Animal Center and the protocol was approved by the local Animal Committee (Organismo preposto al benessere degli animali, OPBA) of SISSA, Italy.
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Supplementary file 1 Supplementary Figure 1. The cartoon schematizes the histological processing. Spinal cords, fixed in PFA, were cryosected rostrocaudally from L4 level. Serial 15 µm thick sections were processed alternatively for staining with cresyl violet or H3R selective immunostaining. After immunohistochemical labelling, slices were then counterstained with haematoxylin to visualize cell nuclei. (TIF 742 kb)
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Coslovich, T., Della Mora, A., D’Angelo, G. et al. Histamine H3 Receptors Expressed in Ventral Horns Modulate Spinal Motor Output. Cell Mol Neurobiol (2020). https://doi.org/10.1007/s10571-020-00831-4
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