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

## TL;DR

This study shows that teneurin-2 and related proteins are upregulated in reactive astrocytes after inducing epilepsy in rats.

## Contribution

The novel finding is the modulation of the teneurin-ADGRL system in reactive astrocytes following status epilepticus.

## Key findings

- Ten-2 and ADGRL1 immunoreactivity increased in the somatosensory area and hippocampus after status epilepticus.
- Ten-2, TCAP-2, and ADGRL1 gene expression was significantly upregulated in the cerebral cortex and CA3 regions.
- Ten-2 and ADGRL1 co-localized in reactive astrocytes in areas with neuronal degeneration.

## Abstract

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.

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.

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.

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.