'Love hormone' oxytocin could be used to treat cognitive disorders like Alzheimer's
July 20, 2020
Science Daily/Tokyo University of Science
Alzheimer's disease progressively degrades a person's memory and cognitive abilities, often resulting in dementia. Amid efforts to find novel treatments for this disease, a recent breakthrough study by scientists from Japan shows that oxytocin―the hormone that we commonly know to induce feelings of love and well-being―can also effectively reverse some of the damage caused by amyloid plaques in the learning and memory center of the brain in an animal model of Alzheimer's.
Alzheimer's disease is a progressive disorder in which the nerve cells (neurons) in a person's brain and the connections among them degenerate slowly, causing severe memory loss, intellectual deficiencies, and deterioration in motor skills and communication. One of the main causes of Alzheimer's is the accumulation of a protein called amyloid β (Aβ) in clusters around neurons in the brain, which hampers their activity and triggers their degeneration. Studies in animal models have found that increasing the aggregation of Aβ in the hippocampus―the brain's main learning and memory center―causes a decline in the signal transmission potential of the neurons therein. This degeneration affects a specific trait of the neurons, called "synaptic plasticity," which is the ability of synapses (the site of signal exchange between neurons) to adapt to an increase or decrease in signaling activity over time. Synaptic plasticity is crucial to the development of learning and cognitive functions in the hippocampus. Thus, Aβ and its role in causing cognitive memory and deficits have been the focus of most research aimed at finding treatments for Alzheimer's.
Now, advancing this research effort, a team of scientists from Japan, led by Professor Akiyoshi Saitoh from the Tokyo University of Science, has looked at oxytocin, a hormone conventionally known for its role in the female reproductive system and in inducing the feelings of love and well-being. "Oxytocin was recently found to be involved in regulating learning and memory performance, but so far, no previous study deals with the effect of oxytocin on Aβ-induced cognitive impairment," Prof Saitoh says. Realizing this, Prof Saitoh's group set out to connect the dots.
Prof Saitoh and team first perfused slices of the mouse hippocampus with Aβ to confirm that Aβ causes the signaling abilities of neurons in the slices to decline or―in other words―impairs their synaptic plasticity. Upon additional perfusion with oxytocin, however, the signaling abilities increased, suggesting that oxytocin can reverse the impairment of synaptic plasticity that Aβ causes.
To find out how oxytocin achieves this, they conducted a further series of experiments. In a normal brain, oxytocin acts by binding with special structures in the membranes of brain cells, called oxytocin receptors. The scientists artificially "blocked" these receptors in the mouse hippocampus slices to see if oxytocin could reverse Aβ―induced impairment of synaptic plasticity without binding to these receptors. Expectedly, when the receptors were blocked, oxytocin could not reverse the effect of Aβ, which shows that these receptors are essential for oxytocin to act.
Oxytocin is known to facilitate certain cellular chemical activities that are important in strengthening neuronal signaling potential and formation of memories, such as influx of calcium ions. Previous studies have suspected that Aβ suppresses some of these chemical activities. When the scientists artificially blocked these chemical activities, they found that addition of oxytocin addition to the hippocampal slices did not reverse the damage to synaptic plasticity caused by Aβ. Additionally, they found that oxytocin itself does not have any effect on synaptic plasticity in the hippocampus, but it is somehow able to reverse the ill―effects of Aβ.
Prof Saitoh remarks, "This is the first study in the world that has shown that oxytocin can reverse Aβ-induced impairments in the mouse hippocampus." This is only a first step and further research remains to be conducted in vivo in animal models and then humans before sufficient knowledge can be gathered to reposition oxytocin into a drug for Alzheimer's. But, Prof Saitoh remains hopeful. He concludes, "At present, there are no sufficiently satisfactory drugs to treat dementia, and new therapies with novel mechanisms of action are desired. Our study puts forth the interesting possibility that oxytocin could be a novel therapeutic modality for the treatment of memory loss associated with cognitive disorders such as Alzheimer's disease. We expect that our findings will open up a new pathway to the creation of new drugs for the treatment of dementia caused by Alzheimer's disease."
https://www.sciencedaily.com/releases/2020/07/200720093308.htm
Mothers' behavior influences bonding hormone oxytocin in babies
October 17, 2019
Science Daily/Max Planck Institute for Human Cognitive and Brain Sciences
A new epigenetic study now suggests that mothers' behavior can also have a substantial impact on their children's developing oxytocin systems.
Oxytocin is an extremely important hormone, involved in social interaction and bonding in mammals, including humans. It helps us relate to others. It strengthens trust, closeness in relationships, and can be triggered by eye contact, empathy, or pleasant touch. It's well known that a new mother's oxytocin levels can influence her behavior and as a result, the bond she makes with her baby. A new epigenetic study by Kathleen Krol and Jessica Connelly from the University of Virginia and Tobias Grossmann from the Max Planck Institute for Human Cognitive and Brain Sciences now suggests that mothers' behavior can also have a substantial impact on their children's developing oxytocin systems.
Childhood marks a dynamic and malleable phase of postnatal development. Many bodily systems are coming online, maturing, or getting tweaked, often setting our psychological and behavioral trajectories well into adulthood. Nature plays an obvious role, shaping us through our genes. But we are also heavily influenced by our interactions, with other people and with our environment. "It is well known that oxytocin is actively involved in early social, perceptual, and cognitive processes, and, that it influences complex social behaviors," says Tobias Grossmann. "However, in this study we ask whether the mother's behavior might also have a decisive influence on the development of the baby's oxytocin system itself. Advances in molecular biology, epigenetics in particular, have recently made it possible to investigate the interaction of nature and nurture, in this case infant care, in fine detail. That is exactly what we've done here."
The scientists observed a free play interaction between mothers and their five-month-old children. "We collected saliva samples from both the mother and the infant during the visit and then a year later, when the child was 18 months old. We were interested in exploring whether the involvement of the mother, in the original play session, would have an influence on the oxytocin receptor gene of the child, a year later. The oxytocin receptor is essential for the hormone oxytocin to exert its effects and the gene can determine how many are produced," explains Kathleen Krol, a Hartwell postdoctoral fellow in Connelly's Lab at the University of Virginia who conducted the study together with Tobias Grossmann at MPI CBS in Leipzig.
"We found that epigenetic changes had occurred in infant's DNA, and that this change was predicted by the quality of the mother's involvement in the play session. If mothers were particularly involved in the game with their children, there was a greater reduction in DNA methylation of the oxytocin receptor gene one year later. Decreased DNA methylation in this region has previously been associated with increased expression of the oxytocin receptor gene. Thus, greater maternal involvement seems to have the potential to upregulate the oxytocin system in human offspring," explains the scientist. "Importantly, we also found that the DNA methylation levels reflected infant temperament, which was reported to us by the parents. The children with higher methylation levels at 18-months, and presumably lower levels of oxytocin receptor, were also more temperamental and less well balanced."
The results of this study provide a striking example of how we are not simply bound by our genes but are rather the products of a delicate interplay between our blue prints and experiences. Early social interaction with our caregivers, certainly not excluding fathers, can influence our biological and psychological development through epigenetic changes to the oxytocin system. These and related findings highlight the importance of parenting in promoting cross-generational health.
https://www.sciencedaily.com/releases/2019/10/191017111705.htm