Abstract

The trigeminal system is key to the pathophysiology of migraine and cluster headache, two primary headache disorders that share many features. Recently, MER proto-oncogene tyrosine kinase (MERTK), a cell surface receptor, was strongly associated with cluster headache through genetic studies. Further, the MERTK ligand galectin-3 has been found to be elevated in serum of migraine patients. In this study, MERTK and MERTK ligands were investigated in key tissue to better understand their potential implication in the pathophysiology of primary headache disorders. Immunohistochemistry was used to map MERTK and galectin-3 expression in rat trigeminal ganglia. RT-qPCR was used to assess MERTK gene expression in blood, and ELISA immunoassays were used for MERTK ligand quantification in serum from study participants with and without cluster headache. MERTK gene expression was elevated in blood samples from study participants with cluster headache compared to controls. In addition, MERTK ligand galectin-3 was found at increased concentration in the serum of study participants with cluster headache, whereas the levels of MERTK ligands growth arrest specific 6 and protein S unaffected. MERTK and galectin-3 were both expressed in rat trigeminal ganglia. Galectin-3 was primarily localized in smaller neurons and to a lesser extent in C-fibres, while MERTK was found in satellite glia cells and in the outer membrane of Schwann cells. Interestingly, a strong MERTK signal was found specifically in the region proximal to the nodes of Ranvier. The overexpression of MERTK and galectin-3 in tissue from study participants with cluster headache, as well as the presence of MERTK in rat peripheral satellite glia cells and Schwann cells in the trigeminal ganglia, further highlights MERTK signalling as an interesting potential future therapeutic target in primary headache.

Details

Title
MERTK in the rat trigeminal system: a potential novel target for cluster headache?
Author
Edvinsson, Jacob C. A. 1 ; Ran, Caroline 2 ; Olofsgård, Felicia Jennysdotter 2 ; Steinberg, Anna 3 ; Edvinsson, Lars 1 ; Belin, Andrea Carmine 2 

 Lund University, Department of Internal Medicine, Lund, Sweden (GRID:grid.4514.4) (ISNI:0000 0001 0930 2361) 
 Karolinska Institutet, Centre for Cluster Headache, Department of Neuroscience, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
 Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Karolinska University Hospital, Department of Neurology, Stockholm, Sweden (GRID:grid.24381.3c) (ISNI:0000 0000 9241 5705) 
Pages
85
Publication year
2024
Publication date
Dec 2024
Publisher
Springer Nature B.V.
ISSN
11292369
e-ISSN
11292377
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3059152766
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.