Intracerebroventricular administration of oxytocin and intranasal administration of the oxytocin derivative improve β‐amyloid peptide (25–35)‐induced memory impairment in mice

Abstract

Abstract Aim We previously reported that oxytocin, a peptide hormone, can reverse the β‐amyloid peptide (25–35) (Aβ25–35)‐induced impairments of the murine hippocampal synaptic plasticity. In this study, we examined the effects of oxytocin on the Aβ25–35‐induced impairment of cognitive behavior in murine in order to investigate the potential of oxytocin as a clinical treatment tool for Alzheimer's disease (AD). Methods The Y‐maze and Morris water maze (MWM) tests were performed. Since the intracerebroventricular (ICV) administration is both invasive and impractical, we further utilized intranasal (IN) delivery to the brain. For this purpose, we prepared an oxytocin derivative containing cell‐penetrating peptides and a penetration accelerating sequence, which was subsequently used in our IN administration experiments. Results We herein showed that the ICV administration of oxytocin in mice exerted memory‐improving effects on the Aβ25–35‐induced amnesia in both the Y‐maze and MWM tests. The IN administration of the oxytocin derivative exhibited memory‐improving effects in the Y‐maze test. Moreover, we acquired evidence that the fluorescein isothiocyanate‐labeled oxytocin derivative was distributed throughout the mouse brain following its IN administration. Conclusion Our results suggest that the oxytocin derivative is effective for its IN delivery to the brain and may be particularly useful in the clinical treatment of cognitive impairment, such as that characterizing AD.

Keywords

• amnesia
• brain drug delivery and targeting
• intranasal administration
• oxytocin
• spatial memory
• β‐amyloid peptide (25–35)