Japanese researchers led by Professor Akiyoshi Saitoh from the Tokyo University of Science have published new research that explores the potential of oxytocin as a therapy to combat cognitive disorders such as Alzheimer’s disease.
Oxytocin is often called the love hormone, given its role in the reproductive system and its role in creating feelings such as love, well-being, and trust. Oxytocin is also known to decrease with age, and researchers such as Dr. Irina Conboy have explored its role in aging [1]. Oxytocin is known to activate MAP kinase, a pathway that plays an important role in aging and tissue regeneration [2].
More recently, it was discovered that it is also involved in learning and cognitive performance, so the researchers of this new study wanted to explore the effects of oxytocin on amyloid beta (Aβ)-induced cognitive impairment, typically seen in Alzheimer’s disease [3].
In order to see how Aβ impairs cognition, the team initially circulated Aβ through slices of mouse hippocampus to see how it impacted the signaling capacity of the neurons in the tissue. Next, they circulated oxytocin through the same brain slices and observed that neuron signaling improved, suggesting that the oxytocin was able to reverse the signaling impairment caused by Aβ.
In a healthy brain, oxytocin acts by binding to oxytocin receptors, structures located in the membranes of neurons. The researchers’ next step was to inhibit these receptors in the brain slices to see if oxytocin could reverse the cognitive impairment that Aβ causes without being able to bind to the oxytocin receptors.
In other words, could oxytocin reverse the impairment simply by its presence? The answer was, perhaps unsurprisingly, no. These results confirmed that the oxytocin receptors are a critical part of the reversal process.
Oxytocin is known to play an important role in neuronal signaling strength and in facilitating the creation of memories via a number of chemical interactions, including the influx of calcium ions. Previous studies suggest that Aβ disrupts these chemical interactions, and when the researchers artificially blocked them, they found that the addition of oxytocin did not reverse Aβ impairment. This means that oxytocin relies on these chemical interactions to reverse the damage.
Oxytocin, a peptide hormone synthe[prisna-wp-translate-show-hide behavior=”show”][/prisna-wp-translate-show-hide]sized in the hypothalamic paraventricular nucleus, has been reported to participate in the regulation of learning and memory performance. However, no report has demonstrated the effect of oxytocin on the amyloid-beta (Aβ)-induced impairment of synaptic plasticity. In this study, we examined the effects of oxytocin on the Aβ-induced impairment of synaptic plasticity in mice.
We found that oxytocin reversed the impairment of LTP induced by Aβ25-35 perfusion in the mouse hippocampus. These effects were blocked by pretreatment with the selective oxytocin receptor antagonist L-368,899. Furthermore, the treatment with the ERK inhibitor U0126 and selective Ca2+-permeable AMPA receptor antagonist NASPM completely antagonized the effects of oxytocin.
Conclusion
This study is the first of its kind in showing that oxytocin can reverse Aβ-induced cognitive impairment. The usual caveats apply, of course: this is in mice, it is at a very early stage of research, and more in vivo studies must be conducted prior to moving to human trials.
That said, given that there are currently no effective treatments for Alzheimer’s disease available yet, this line of research presents a novel approach to treating the condition.
Literature
[1] Mehdipour, M., Etienne, J., Chen, C. C., Gathwala, R., Rehman, M., Kato, C., … & Conboy, I. M. (2019). Rejuvenation of brain, liver and muscle by simultaneous pharmacological modulation of two signaling determinants, that change in opposite directions with age. Aging (Albany NY), 11(15), 5628.
[2] Yousef, H., Conboy, M. J., Mamiya, H., Zeiderman, M., Schlesinger, C., Schaffer, D. V., & Conboy, I. M. (2014). Mechanisms of action of hESC-secreted proteins that enhance human and mouse myogenesis. Aging (Albany NY), 6(8), 602.
[3] Takahashi, J., Yamada, D., Ueta, Y., Iwai, T., Koga, E., Tanabe, M., … & Saitoh, A. (2020). Oxytocin reverses Aβ-induced impairment of hippocampal synaptic plasticity in mice. Biochemical and Biophysical Research Communications.
