Results show comparisons between intranasal and intracerebroventricular distribution of an oxytocin derivative.
A study found that intranasal (IN) delivery of an oxytocin derivative to the brain may be an effective treatment for cognitive disorders such as Alzheimer disease.
Leveraging previous research suggesting that introducing cell-penetrating peptides (CPPs) and a penetration-accelerating sequence (PAS) via structural modifications can benefit the nose-to-brain delivery pathway, the investigators created the oxytocin derivative PAS-CPPs-oxytocin. Their goal was to see if IN delivery of this oxytocin derivative would help improve cognitive function in mice similarly to the more invasive intracerebroventricular (ICV) administration method.1
“We have previously shown that oxytocin reverses amyloid 𝛽 peptide (25-35) (A𝛽25-35)-induced impairment of synaptic plasticity in rodents,” said corresponding author Jun-Ichiro Oka, PhD, in a press release. “We wanted to see if PAS-CPPs-oxytocin could be delivered more efficiently to the mouse brain for clinical application, and if it improved cognitive functional behavior in mice.”2
The investigators conducted Y-maze and Morris water maze (MWM) tests and found that ICV delivery of oxytocin showed memory-improving effects on the Aβ25–35-induced amnesia in both the Y-maze and MWM tests, while IN administration of the oxytocin derivative showed memory-improving effects in the Y-maze test. The investigators also found evidence that, following its IN administration, the fluorescein isothiocyanate-labeled oxytocin derivative was distributed throughout the brain.1
“My team is the first to show that the oxytocin derivative can improve the A𝛽25-35-induced memory impairment in mice,” Oka said in a press release. “This suggests that oxytocin may help reduce the cognitive decline we see in Alzheimer’s disease.”2
Oka, who is on the faculty of pharmaceutical sciences at Tokyo University of Science, further clarified that these findings are clinically useful because “the oxytocin derivative enters the brain more efficiently. Furthermore, since IN delivery is a non-invasive procedure, this modified version of the hormone could potentially be a clinically viable treatment for Alzheimer’s disease.”2
1. Takahashi J, Ueta Y, Yamada D, et al. Intracerebroventricular administration of oxytocin and intranasal administration of the oxytocin derivative improve β-amyloid peptide (25-23)-induced memory impairment in mice. Neyropsychopharmacol Rep. 2022;00:1-10.
2. Novel derivative of “love hormone” oxytocin improves cognition impairment in Alzheimer’s. Toyko University of Science. News release. October 24, 2022. Accessed November 4, 2022. https://www.tus.ac.jp/en/mediarelations/archive/20221021_1000.html