The Role of Teneurin C-terminal Associated Peptide (TCAP)-1 in the Regulation of Stress-related Behaviours

The teneurin C-terminal associated peptides (TCAPs) are a newly-elucidated family of four bioactive peptides that were found during a screen for novel corticotropin-releasing factor (CRF)-like peptide families. The predicted peptide sequences have the characteristics of a bioactive peptide and are 40 or 41 amino acid residues long. One of the peptides in the family, TCAP-1, has numerous in vitro effects, where it modulates cAMP accumulation, neuronal proliferation, neurite outgrowth, brain-derived neurotrophic factor levels, and possesses neuroprotective effects under alkalotic or hypoxic conditions. However, little is known about TCAP-1’s in vivo effects. Given the structural similarity of TCAP-1 to the CRF family, it is expected that these peptide systems may interact in vivo. The aims of this research were to 1) investigate the role of TCAP-1 on CRF- and stress-induced behaviours in rats, and determine if intracerebral TCAP-1 could modulate stress-induced anxiety-like behaviours; 2) determine the areas of the brain where TCAP-1 is taken up and is active; and 3) investigate the role of TCAP-1’s cytoskeletal modulation on stress-sensitive areas of the brain so as to determine a mechanism for long-term behavioural changes in the brain. I have established that TCAP-1 modulates anxiety-like behaviour in exploratory tests of anxiety, and that TCAP-1 is particularly active in the limbic system, including the hippocampus, amygdala, septum, and medial prefrontal cortex, and that TCAP-1 increases the dendritic spine density in the hippocampus, a brain area important for anxiety, learning, and memory. These studies have confirmed that TCAP-1 indeed plays a role in stress-like behaviours and modulates stress-related processes in the brain.Ph