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Developmental Biology - Alzheimer's
The Love Hormone "Oxytocin" Could Treat Alzheimer's
Oxytocin could be a potential new therapeutic option for cognitive disorders such as Alzheimer's diseas...
The "Love hormone" oxytocin might be useful in treating cognitive disorders like Alzheimer's say scientists. For the first time it has been discovered that oxytocin is a potential new therapeutic option for cognitive disorders.
Alzheimer's is a progressive disorder of the nerve cells (neurons) in the brain where connections between neurons degenerate. This slow process causes severe memory loss, intellectual deficiencies, and eventual deterioration of motor skills, including communication skills.
One of the main causes of Alzheimer's is the accumulation of a protein called amyloid ß (Aß) in clusters around neurons in the brain, which hampers their activity and triggers their degeneration. Studies in animals have found increasing aggregations of Aß in the hippocampus - the main learning and memory center of the brain - causes a decline in neural signal transmissions.
This degeneration specifically affects a trait called "synaptic plasticity" - the ability of synapses (signal exchange between neurons) to adapt to an increase or decrease in signaling over time. Synaptic plasticity is crucial to the development of learning and cognitive functions in the hippocampus. Aß and its role in causing cognitive memory deficits has been the focus of most research aimed at treating 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 Aß-induced cognitive impairment."
Akiyoshi Saitoh PhD, Professor, Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan
Realizing this, Prof Saitoh's group set out to connect the dots. Their work is published in the journal: Biochemical and Biophysical Research Communications.
The team first perfused slices of mouse hippocampus with Aß to confirm it caused neural signaling abilities to decline, impairing synaptic plasticity.
However, upon adding a perfusion of oxytocin, all signaling abilities increased, suggesting oxytocin can reverse the impairment that Aß 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 Aß-induced impairment of synaptic plasticity without binding to these receptors. Expectedly, when the receptors were blocked, oxytocin could not reverse the effect of Aß, 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 Aß 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 Aß. 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 A.
"This is the first study in the world that has shown that oxytocin can reverse Aß-induced impairments in the mouse hippocampus."
Akiyoshi Saitoh PhD.
This is only a first step and further research remains to be conducted in vivo with animal models, followed by human testing before a drug treatment for Alzheimer's can be advised. But, Prof Saitoh remains hopeful.
"At present, there are no sufficiently satisfactory drugs to treat dementia, and new therapies with novel mechanisms 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."
Akiyoshi Saitoh PhD.
Abstract Aim
Oxytocin, a peptide hormone synthesized 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 (A?)-induced impairment of synaptic plasticity. In this study, we examined the effects of oxytocin on the A?-induced impairment of synaptic plasticity in mice.
Methods
To investigate the effect of oxytocin on synaptic plasticity, we prepared acute hippocampal slices for extracellular recording and assessed long-term potentiation (LTP) with perfusion of the A? active fragment (A?25-35) in the absence and presence of oxytocin.
Results
We found that oxytocin reversed the impairment of LTP induced by A?25-35 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 is the first report to demonstrate that oxytocin could reverse the effects of A? on hippocampal LTP in mice. We propose that ERK phosphorylation and Ca2+-permeable AMPA receptors are involved in this effect of oxytocin.
Authors
Junpei Takahashia, Daisuke Yamadaa, Yudai Ueta, Takashi Iwai, Eri Kogaa, Mitsuo Tanabe, Jun-Ichiro Oka and Akiyoshi Saitoh.
Acknowledgements
About the Tokyo University of Science
Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators.
With a mission of "Creating science and technology for the harmonious development of nature, human beings, and society", TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.
About Professor Akiyoshi Saitoh from the Tokyo University of Science
Dr Akiyoshi Saitoh is a Professor at the Faculty of Pharmaceutical Sciences, Tokyo University of Science. A respected and senior researcher with more than 25 years of experience, he has more than 100 research publications to his credit and is the lead author of this paper. His chief areas of interest include medicinal pharmacology, behavioral pharmacology, and neuroscience, including the role of the amygdala in the fear extinction memory in rodents and the development of a novel opioid delta receptor agonist for antidepressants/anxiolytics. He also has patents for drugs in this area.
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Jul 29 2020 Fetal Timeline Maternal Timeline News
 Oxytocin, the hormone that induces feelings of love and well-being, is found to reverse some of the damage caused by amyloid plaques in the learning and memory center of the brain. CREDIT Tokyo University of Science
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