Evaluation of kisspeptin transport across the blood–brain barrier after intranasal administration

BACKGROUND: The kisspeptin family (KISS1), encoded by the kiss1 gene, is among the newly identified yet underexplored peptide families in terms of efficacy and intranasal delivery. Kisspeptins are involved not only in reproductive function but also in behavioral, emotional, and cognitive processes. Efficient delivery of kisspeptins to the central nervous system could open new perspectives for their application. AIM: The work aimed to evaluate the efficacy of kisspeptin-10 transport across the blood–brain barrier after intranasal administration. METHODS: The study included 45 outbred mice. Animals received kisspeptin-10 intranasally at doses of 0.1, 1, and 10 μg, and intraperitoneally at doses of 1, 10, and 100 μg. Animal behavior was assessed using the open field test, elevated plus maze, and sexual motivation test. RESULTS: In the present study, stable and dose-dependent effects of kisspeptin-10 on mouse behavior were observed after intranasal administration. Intranasal kisspeptin-10 induced statistically significant increases in sexual motivation, horizontal and vertical locomotor activity, reduced anxiety, and enhanced exploratory behavior in sexually mature male mice. The most pronounced behavioral changes were produced by the 10 μg dose, exerting central effects after intranasal administration compared with the groups receiving intraperitoneal administration. In contrast, intraperitoneal kisspeptin-10 at doses of 1 μg and 10 μg produced virtually no behavioral changes. Increasing the intraperitoneal dose to 100 μg resulted in statistically significant behavioral changes; however, the effect was less pronounced than that observed after intranasal administration of 10 μg. CONCLUSION: Statistically significant behavioral changes following intranasal administration required concentrations 10-fold lower than those needed for peripheral administration. Given the evident effects of intranasal kisspeptin-10 in each behavioral test, it can be assumed that kisspeptin-10 penetrated the brain, bypassing the blood–brain barrier, and exerted central effects. These findings support the potential feasibility and importance of this delivery route for targeting the central nervous system.