Oxytocin, often referred to as the “love hormone” due to its association with pair bonding, is a powerful hormone that functions as a neurotransmitter in the brain. It plays an important role in reproduction, initiating contractions before birth as well as milk release and is thought to be involved in broader social cognition and behaviour, potentially ranging from mother-infant bonding and romantic connection to group-related attitudes and prejudice. In another positive step towards the alleviation of Alzheimer’s disease, a leading cause of dementia, scientists from Japan conducted a study suggesting that an oxytocin derivative may help reduce the cognitive decline we see in Alzheimer’s disease. – Nadya Swart
Novel Derivative of “Love Hormone” Oxytocin Improves Cognitive Impairment in Alzheimer’s
Scientists from Japan show how the intranasally delivered oxytocin derivative could be used to treat Alzheimer’s disease
Alzheimer’s disease (AD), characterised by an accumulation of β-amyloid protein (Aβ) in brain tissue, is a leading cause of dementia. Researchers at Tokyo University of Science have previously reported on the oxytocin-induced reversal of impaired synaptic plasticity triggered by amyloid β peptide (25-35) (Aβ(25–35)). They now show that an oxytocin derivative with modifications to enhance brain perfusion can reverse Aβ(25–35)-induced cognitive impairment in mice.
The cognitive decline and memory loss observed in Alzheimer’s disease (AD) is attributed to the accumulation of β-amyloid protein (Aβ), which impairs neural function in the brain. Experimentation has shown that oxytocin, a peptide hormone primarily responsible for parturition, bonding, and lactation, also regulates cognitive behaviour in the rodent central nervous system (CNS). This finding, along with the identification of oxytocin receptors in CNS neurons, has spurred interest in the potential role of oxytocin in reversing memory loss tied to cognitive disorders like AD.
However, peptides like oxytocin are characterised by weak blood-brain barrier permeability, and so can only be efficiently delivered to the brain via intracerebroventricular (ICV) administration. ICV, however, is an invasive technique which is impractical to implement clinically.
Delivering peptides to the CNS via intranasal (IN) administration is a viable clinical option. Prof. Chikamasa Yamashita at Tokyo University of Science recently patented a method to increase the efficiency of peptide delivery to the brain, by introducing cell-penetrating peptides (CPPs) and a penetration accelerating sequence (PAS) through structural modifications. Previous work had confirmed that both CPPs and the PAS benefit the nose-to-brain delivery pathway. Now, a group of researchers, led by Prof. Akiyoshi Saitoh and Prof. Jun-Ichiro Oka, leveraged this approach to prepare an oxytocin derivative: PAS-CPPs-oxytocin. Their findings were published online in Neuropsychopharmacology Reports on 19 September 2022.
“We have previously shown that oxytocin reverses amyloid 𝛽 peptide (25-35) Aβ(25–35)-induced impairment of synaptic plasticity in rodents. 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 behaviour in mice,” states Prof. Oka.
The group first developed an Aβ(25–35) peptide-induced amnesia model by supplying Aβ(25–35) to the mouse brain using ICV delivery. During the course of the study, the spatial working and spatial reference memories of these mice were evaluated using the Y-maze and Morris water maze (MWM) tests. After confirming that memory was affected in Aβ(25–35)-impaired mice, PAS-CPPs-oxytocin and native oxytocin were administered using the IN and ICV routes respectively, to see if learning and memory improved in the treated mice. Finally, the distribution of the IN-administered oxytocin derivative in brain tissue was profiled by imaging of a fluorescent-tagged oxytocin derivative.
The results of this study were quite promising! The tagged PAS-CPPs-oxytocin showed distribution throughout the mouse brain following its IN administration. While the ICV administration of native oxytocin improved test outcomes in both the Y-maze and MWM tests, the IN administered PAS-CPPs-oxytocin yielded memory improving effects in the Y-maze test. Hailing the team’s discovery, Prof. Oka says, “My team is the first to show that the oxytocin derivative can improve the Aβ(25–35)-induced memory impairment in mice. This suggests that oxytocin may help reduce the cognitive decline we see in Alzheimer’s disease.”Why are these findings clinically useful? Prof. Oka explains the broader implications of their work, “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.”
Read Also:
- Dr Jackie Stone’s persecution another attempt to stop ivermectin
- SA’s activist lawyer Erin Richards says compelling evidence and Pfizer’s own data shows it lied by claiming Covid vaccine was “safe and effective”
- Pfizer used Israel as “the world’s first laboratory” to study its Covid vaccine’s efficacy, NOT promote safety