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ORIGINAL RESEARCH article

Front. Neurosci.

Sec. Neurodegeneration

Teneurin-2 and related proteins in reactive astrocytes after status epilepticus induction in adult rats

  • 1. School of Dentistry of Araçatuba, São Paulo State University (UNESP), Araçatuba, Brazil

  • 2. Anatomy Division, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, Brazil

  • 3. University Center in the North of São Paulo (UNORTE),, São José do Rio Preto, Brazil

  • 4. Department of Cell and Systems Biology, University of Toronto, Toronto, Canada

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Abstract

Introduction: Teneurins are a protein family composed of four paralogs in vertebrates (Ten-1-4), expressed mainly in the central nervous system (CNS), which primarily participate in neuronal circuit establishment through homophilic or heterophilic interactions. These proteins possess a bioactive peptide, teneurin C-terminal associated peptide (TCAP1-4), located at the distal extracellular tip. The adhesion G protein-coupled receptors L (ADGRL1-3) are the main receptors for teneurins. The purpose of this study was to evaluate the Ten-2/TCAP-2/ADGRL1 system in the cerebral cortex and hippocampus in a rat model of epilepsy. Methods: Adult male rats received LiCl-pilocarpine and were euthanized 2, 5, 14, 35 and 65 days after status epilepticus (SE) induction. Ten-2, TCAP-2 and ADGRL1 immunohistochemistry and quantitative gene expression were performed in the primary somatosensory area and hippocampus. Fluoro-Jade C staining was used to verify colocalization between neuronal degeneration and immunoreactive cells. Results: Increases in Ten-2- (Ten-2-LI) and ADGRL1-like immunoreactive (ADGRL1-LI) reactive astrocyte profiles were mainly found in the primary somatosensory (5 days after SE, p < 0.0001) and CA3 (2, 5 and 14 days, p < 0.0001) areas, when compared with other groups. Ten-2, TCAP-2 and ADGRL1 gene expressions showed significant up-regulation in the cerebral cortex (5 days, p <0.001) and CA3 (2 and 5 days, p < 0.0001). Ten-2-LI and ADGRL1-LI were colocated in the same reactive astrocyte profiles, positioned in brain regions with neuronal degeneration. Conclusion: This study demonstrated that SE induced an up-regulation of Ten-2, TCAP-2 and ADGRL1 in reactive astrocytes of adult rats, indicating that the astrocytic teneurin-ADGRL system is modulated after status epilepticus induction.

Summary

Keywords

adhesion G protein-coupled receptor, adult rat, Epilepsy, Pilocarpine, reactiveastrocytes, Status Epilepticus, TCAP, Teneurin

Received

21 July 2025

Accepted

26 December 2025

Copyright

© 2025 Tessarin, Hogg, Gonçalves, Casatti, Savenhago, Costa, Del Priore, Lovejoy, Horta-Junior and Casatti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Gestter Willian Lattari Tessarin

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