A new groundbreaking study provides another biochemical explanation of why people with dementia need a lot of personal closeness and care.
Oxytocin is a cyclic neuropeptide produced by many mammals in the paraventricular nucleus of the hypothalamus. In addition to its importance for the birth process and social binding behavior, its involvement in the regulation of learning and memory has also been described recently. A recent study recently revealed an amazing effect of oxytocin: it is able to reverse cognitive disorders induced by the amyloid-beta (Aβ).1,2
Oxytocin triggers feelings of love and well-being - but it can apparently do much more. A pathomechanism described in previous work in Alzheimer's disease is the loss of synaptic plasticity of the hippocampal neurons through the accumulation of amyloid-beta. For cognitive performance and learning processes, neuronal plasticity, i.e. the potential of the synapses to adapt to increasing or decreasing signal activities over time, is essential.
A team of researchers from the Tokyo University of Science found that this ability to process signals increases again in the hippocampus of mice under oxytocin as if the amyloid-related damage were reversible under its influence. To date, there have been no studies on this because the evidence that oxytocin plays a role in learning and memory processes is relatively new.
To find out where this hormone effect comes from, the researchers selectively blocked the receptors for oxytocin in a follow-up experiment. As expected, oxytocin was unable to restore the plasticity disturbed by Aβ after this pretreatment. The administration of an ERK inhibitor and a selective antagonist against a subtype of glutamate receptors (calcium-permeable AMPA receptor, which is important for neuronal plasticity) had a similar effect. These interventions completely antagonized the action of oxytocin.
This is consistent with previous work describing the role of oxytocin in biochemical activities that support nerve conduction and memory formation, such as the influx of calcium ions.
Previous studies have suggested that amyloid beta suppresses some of these processes. When the researchers artificially inhibited these biochemical processes in the experiment described above, they could no longer observe a reversal of the Aβ-induced pathological changes through oxytocin administration.
Thus, there does not appear to be a direct effect of oxytocin on synaptic plasticity in the hippocampus. Calcium-permeable AMPA-receptors and ERK-phosphorylation seem to be involved in mediating the oxytocin effects.
Professor Akiyoshi Saitoh, head of the research group, says that this is only a first step that needs to be followed by further research, but he believes the approach is promising. "Currently, there are no satisfactory drugs for the treatment of dementia, and new therapies with new mechanisms of action are sought after. Our study shows the interesting possibility that oxytocin could be a new therapeutic approach for the treatment of memory loss associated with cognitive disorders such as M Alzheimer's disease, for example. We hope that our discoveries will open up an unknown pathway to the development of new compounds for the treatment of Alzheimer's dementia" Prof. Saitoh added.
References:
1. Takahashi, J. et al. Oxytocin reverses Aβ-induced impairment of hippocampal synaptic plasticity in mice. Biochemical and Biophysical Research Communications 528, 174-178 (2020).
2. 'Love Hormone' Oxytocin Could Be Used to Treat Cognitive Disorders Like Alzheimer's. Tokyo University of Science https://www.tus.ac.jp/en/.