PACAP-38 unveils a neuro-immune crosstalk in tilapia orchestrated through Oreochromicin-mediated antibacterial defense

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP-38) is a multifunctional neuropeptide known to influence key physiological processes in teleost fish, including somatic growth and immune regulation. Building upon this foundation, our study further characterizes the contribution of PACAP-38 to antibacterial defenses in Nile tilapia. Following intraperitoneal administration of the synthetic peptide, we observed a significant increase in the bacterial growth inhibitory activity of skin and gill mucus against Edwardsiella tarda and Pseudomonas aeruginosa , concomitant with the modulation of Oreochromicins gene expression. Furthermore, PACAP-38 administration, both alone and in combination with a P. aeruginosa bacterin, significantly improved survival rates following an experimental challenge with this pathogen. In a complementary experiment, oral delivery of PACAP-38 via modified feed not only enhanced fish welfare but also reduced the bacterial load of P. aeruginosa in gill mucus post-infection and increased Oreochromicins expression in mucosal tissues. Collectively, these findings demonstrate that PACAP-38 enhances mucosal antibacterial defenses in vivo , solidifying its role as an effective immunomodulatory peptide in teleost. With further development, PACAP-38 presents a promising alternative to conventional antibiotics or inactivated vaccines in aquaculture.