A Putative Role of Teneurin-2 and Its Related Proteins in Astrocytes

Abstract

Teneurins are type II transmembrane proteins comprised of four phylogenetically conserved homologs (Ten-1-4) that are highly expressed during neurogenesis. An additional bioactive peptide named teneurin C-terminal-associated peptide (TCAP-1-4) is present at the carboxyl terminal of teneurins. The possible correlation between the Ten/TCAP system and brain injuries has not been explored yet. Thus, this study examined the expression of these proteins in the cerebral cortex after mechanical brain injury. Adult rats were subjected to cerebral cortex injury by needle-insertion lesion and sacrificed at various time points. This was followed by analysis of the lesion area by immunohistochemistry and conventional RT-PCR techniques. Control animals (no brain injury) showed only discrete Ten-2-like immunoreactive pyramidal neurons in the cerebral cortex. In contrast, Ten-2 immunoreactivity was significantly up-regulated in the reactive astrocytes in all brain-injured groups ( p < 0.0001) when compared to the control group. Interestingly, reactive astrocytes also showed intense immunoreactivity to LPHN-1, an endogenous receptor for the Ten-2 splice variant named Lasso. Semi-quantitative analysis of Ten-2 and TCAP-2 expression revealed significant increases of both at 48 h, 3 days and 5 days ( p < 0.0001) after brain injury compared to the remaining groups. Immortalized cerebellar astrocytes were also evaluated for Ten/TCAP expression and intracellular calcium signaling by fluorescence microscopy after TCAP-1 treatment. Immortalized astrocytes expressed additional Ten/TCAP homologs and exhibited significant increases in intracellular calcium concentrations after TCAP-1 treatment. This study is the first to demonstrate that Ten-2/TCAP-2 and LPHN-1 are upregulated in reactive astrocytes after a mechanical brain injury. Immortalized cerebellar astrocytes expressed Ten/TCAP homologs and TCAP-1 treatment stimulated intracellular calcium signaling. These findings disclose a new functional role of the Ten/TCAP system in astrocytes during tissue repair of the CNS.

Teneurins assemble into presynaptic nanoclusters that promote synapse formation via postsynaptic non-teneurin ligands

“…It is possible that the non-synaptic Tenm3 nanoclusters are associated with synaptic junctions that were not labeled because they are outside of the plane of focus. Alternatively, non-synaptic Tenm3 nanoclusters could be present in other neuronal or non-neuronal compartments (e.g., in astrocytes) 23,55 . In this respect, Tenm3 also resembles neurexins that exhibit a significant non-synaptic and non-neuronal component.…”

Microbiota and Diapause-Induced Neuroprotection Share a Dependency on Calcium But Differ in Their Effects on Mitochondrial Morphology

“…For example, adhesion molecules such as cadherins mediate cell signaling and neuroregeneration ( Hirota et al, 2001 ; Kanemaru et al, 2013 ; Friedman et al, 2015 ; Yulis et al, 2018 ; Punovuori et al, 2021 ). The teneurins are transmembrane proteins fundamental for the development of the nervous system ( Drabikowski et al, 2005 ; Mörck et al, 2010 ; Tucker et al, 2012 ; Topf and Drabikowski, 2019 ) and also are neuroprotective ( Al Chawaf et al, 2007 ; Trubiani et al, 2007 ; Tessarin et al, 2019 ).…”

The Cannabis-Induced Epigenetic Regulation of Genes Associated with Major Depressive Disorder

“…Apart from MDD, TCF4 has also been associated with other psychiatric and neurological disorders, such as bipolar disorder and post-traumatic stress disorder [ 79 , 80 ]. Since the TENM2 and TCF4 genes are abundantly expressed in the central nervous system and especially in brain regions important for depression-related phenotypes, such as the hippocampus and cortex [ 56 , 76 , 81 ], DNAm changes in those genes due to exposure to cannabis or cannabis-derived compounds could also be of importance in future treatments for MDD.…”