Newly-elucidated bioactive peptides regulate corticotropin-releasing factor (CRF) pathways in the brain: the role of the teneurin C-terminal associated peptides (TCAPs)

Abstract

The teneurin C-terminal associated peptides (TCAPs) are a family of four novel endogenous peptides that are expressed in the brain and appear to be expressed in all vertebrates.  TCAPs are 40-41 amino acids long and share about 20% amino acid identity to corticotropin-releasing factor (CRF), a peptide that is released in the brain during periods of stress.  Previous work has shown that TCAP-1 has effects both in vitro and in vivo, modulating cAMP accumulation and cell proliferation, as well as affecting anxiety-like behaviour in rats in the acoustic startle test.  Our newest studies have investigated the role of TCAP-1 in regulating CRF.  Firstly, we used immunohistochemistry to determine if acute or repeated intracerebroventricular (ICV) injections of TCAP-1 could affect CRF-induced c-Fos expression in the brain.  Secondly, we utilized two tests of anxiety, the elevated plus maze and the open field, to investigate the effect of TCAP-1 on CRF-induced anxiety-like behaviour.  Our results indicate that TCAP-1 attenuates CRF-induced c-Fos expression in several stress-related areas of the brain, including the hippocampus, amygdala, and medial prefrontal cortex.  However, TCAP-1 did not affect CRF-induced c-Fos expression in other stress-related areas, including the paraventricular nucleus of the hypothalamus and the locus coeruleus, indicating a specificity of the TCAP-1 effect.  Behaviourally, TCAP-1 appeared to modulate CRF-induced behaviour in the elevated plus maze and open field tests.  These studies indicate that the novel peptide, TCAP-1, may be involved in the regulation of CRF, and thus be a new target in the treatment of stress and anxiety disorders.