'Orgasm hormone' restores the sense of smell… Could it fix brain function?

When we turn eight, our brain reaches the end of its phase of intensive growth. To make matters worse, neurons and synapses that are seldom used begin to die. When it comes to the brain, everything functions as in a paraphrase of the Gospel: "the neurons that have a lot will get more, and those that don’t have too much will lose even the little they have." Why is this and what is it all about? We would like to know if anything can reverse this process.

The brain is a miracle. But the most wonderful thing about it is that it is constantly evolving. Not just in early childhood during that period of intensive growth, but also in adulthood. Even in old age, we can still study, do a doctorate, learn carpentry or how to drive, play an instrument or acquire a foreign language. Of course, this does not always apply -- nor can everyone do it with the same success. However, it is certain that every brain must be malleable, otherwise we would not survive in this world -- we would not be able to constantly adapt to a changing environment that rarely pampers us.

We start our intensive education at the end of infancy, around the age of three, very quickly learning to speak and function socially in a group. This is usually on a peer-to-peer basis, although much more would have been picked up from our older colleagues. Never again in life, however, do we learn at such a rate as we do before reaching age eight.

According to current research, this is when the brain is at its most malleable. All possible neural connections, i.e. new synapses, are being formed and consolidating. Therefore, it makes sense to teach children music, drawing, eurhythmics, dance, foreign languages, syllabic reading, etc. as early as possible. When we turn eight, our brain reaches the end of its phase of intensive growth. To make matters worse, neurons and synapses, if seldom used, begin to die. In fact, when it comes to the brain, everything functions as though in a paraphrase of the Gospel: "the neurons that have a lot will get more, and those that don’t have too much will lose even the little they have." Why is this and what is it all about? We would like to know! Therefore, the search for substances that cause the formation and strengthening of synapses according to the frequency of their use is the key axis of research into brain plasticity.

Herrings instead of chocolate

Scientifically speaking, this research is focused on observing the biological basis of "the brain's ability to self-modify by remodeling its existing neural networks and creating new ones to achieve new functional properties." This capacity to give the brain plasticity also helps the networks and circuits of neurons to stay healthy and stable. The brain’s plasticity is the key to its constant ability to change, remember and learn new things -- i.e. creating and maintaining new synapses, even when old ones have been lost. Thanks to this, even those parts of the brain responsible for certain specific skills can adapt and, with training for specific needs, can start being used differently. This, for example, was how that part of our brain responsible for facial recognition adapted and was able to learn how to recognize letters once lettering was eventually created.

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The latest research on brain plasticity, published in December 2022 in the journal Genes & Development, was conducted by neurobiologists from the largest medical center in the US. They represented such prominent medical institutions as Texas Medical Center: Baylor College of Medicine and Texas Children's Hospital. Led by Prof. Benjamin R. Arenkiel, the researchers set out to examine how brain cells build connections with the new neurons formed in adult brains. Since there are ethical issues related to the study of human brains, as is so often the case, their research was conducted on mice (which is considered permissible).

  The search for the molecules that help new neurons build connections in the adult brain paves the way for improved therapies to address neurodevelopmental disorders and repair neural circuits, for example, that have been damaged by stroke or as a result of an operation. However, the American team limited its research to that part of the brain called the olfactory bulb. This is where chemical odor molecules, bound with receptors in neurons, are initially recognized. Perceiving odors at the level of neurons and molecules was awarded the Nobel Prize over a decade ago, and the process itself is based on the constant generation of new neurons. Put simply, within the olfactory bulb, new neurons, constantly created from stem cells, migrate over long distances to find a suitable place for themselves in order to join the already existing network. This explains why this area of the brain is considered ideal for such research.

The COVID-19 epidemic showed us just how astonishing the olfactory bulb’s plasticity is. Were it not for that, we could have lost our sense of smell forever after the disease passed. Of course, some didn’t regain sensitivity to the exact smells on the same level they had before catching SARS-CoV-2. It depends on how new olfactory neurons, equipped with odor receptor genes, are formed. Of course, many of those who were spared catching the coronavirus, remember how as children they liked different smells and flavors (taste is 80 per cent of the perception of the smell of food after all) than they do today as adults. For many, growing up in our culture today, herring rather than white chocolate is a contemporary preference.

The miraculous effect of oxytocin

Because new olfactory neurons are formed throughout life (unfortunately, they specialize very quickly, so they cannot be "grafted" in place of nerve tissue defects), new synapses must constantly be formed between them and the upper levels of the brain in order that the system can integrate and self-model. Therefore, it was well worth determining what this mysterious substance responsible for the formation of such neural plasticity observable in most of us might be. (True, there are people "deaf to smells"). To the considerable surprise of the Texas researcher scientists, but also to their relief that "it does make sense", the team has discovered this magical substance in the widely known and clinically used peptide neurohormone -- oxytocin.
Oxytocin is administered intravenously or intramuscularly to pregnant women to facilitate uterine contractions and speed up labor. In the photo, a midwife gives an injection to a patient at St. Vincent de Paul in Lille, France. Photo: BSIP/UIG via Getty Images
We know it well too. It is sometimes called the "hugging hormone" and even the "orgasm hormone" because its secretion causes mammals to build bonds with their offspring. It works not only with mothers, but also with fathers, as was studied and proved in mice over a year ago. However, before we have a baby to cuddle, oxytocin is released by both sexes during sexual intercourse. It happens in a positive feedback loop, i.e. the more of it appears, the more of it will secrete. It is also released during childbirth, causing the uterus to contract, and informing the fetus to finally start pushing into this world. Along with other hormones, it is essential during lactation.  Nipple sucking stimulates its further secretion. A similar effect of oxytocin peak can be achieved by women with just a single dose of estrogen.

The breakthrough with oxytocin after more than a hundred years of study resulted in the award of the Nobel Prize in 1955 to Vincent du Vigneaud (for identifying its amino acid sequence and its chemical synthesis in the laboratory). Recently, the scientists of the Baylor College of Medicine discovered that oxytocin levels rise in the olfactory bulb, reaching peak when new neurons join neural networks. The researchers also determined that oxytocin triggers a signaling pathway inside of neurons that promotes the formation of synapses. So, thanks to oxytocin (and its receptor), two newly formed neurons in the mature brain were able to connect with a synapse. Moreover, when the mice were deprived of essential oxytocin activity in the olfactory bulb, the resulting neurons had underdeveloped synapses and impaired function.

So it is not a miracle -- just a mass reaction of newly formed neurons to the hormone! On the one hand, shock and disbelief that all this plasticity (at least in the olfactory brain) works according to a simple rule; on the other hand, some surprise and relief to find that it is oxytocin that causes it. Plasticity is a phenomenon observed in all vertebrates and this hormone would be more suitable as a trigger for it than any other. 

Patriotism or xenophobia, or maybe the stimulus of heroes?

Here it is worth telling a story about the social adaptation of people. For years, oxytocin (administered experimentally intranasally or in rarer cases, in intravenous infusions) has been studied as a neurohormone that builds human bonds in the group and empathy. Thanks to it, we would divide the world into our own (similar to us) and strangers. This is easiest to test by skin tone reactions, e.g. we react more strongly to photos of our group members making pained faces than to photos of a group of outsiders with the same facial expression. We're also more likely to help "our own" rather than "strangers" when they're in pain -- all after an oxytocin "sniff". Also under its influence, we are more likely to lie should that prove beneficial to members of our group.

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The role of oxytocin also emerges when studying conflict between members of different groups. Under its influence, we defend and protect the vulnerable members of the group. We even change our subjective preferences to adapt to the ideals of our circle, instead of the ideals of a foreign community. A study conducted in the Netherlands also found that oxytocin increased favoritism of one's own ethnicity in the population, while decreasing acceptance of other ethnicities and foreigners. People also show greater attachment to their country's flag, remaining indifferent to other cultural signifiers when under the influence of oxytocin. Does this then mean that oxytocin deserves to be called, as some would wish, "the hormone of patriotism", rather than, as others demand, "the hormone of xenophobia"?

It has an overall reinforcing effect on all social emotions as intranasal administration increases jealousy and Schadenfreude. People "on oxytocin" identify expressions of disgust on another person’s face far more quickly a than people who have not been stimulated with this neurohormone. Its role has also been recognized in one of the strongest adaptive reactions of vertebrates, as in fear-flight. Administration of oxytocin reduces fear in rodents, possibly by inhibiting the amygdala in the brain, which is responsible for these responses. In other words, perhaps it is oxytocin that makes us heroes in moments of danger.

Finally, oxytocin affects men and women differently. After taking it, women react faster than men to socially significant stimuli, which is unsurprising, given that estrogens stimulate its formation. And testosterone directly inhibits oxytocin in mice. This may have evolutionary significance since it makes activities such as hunting and attacking invaders mentally easier, insofar as oxytocin is strongly associated with empathy and trusting others in the group.

Now the Texan neurobiologists have been able to show the probable source of this oxytocin effect -- modulating reactions, and perhaps even building bonds and social adaptations. Although it is evident that the formation of new synapses is not something that happens very speedily, the fact is that the oxytocin receptors are formed in new neurons of the adult mouse’s olfactory bulb, and that the peak of this "creation" takes place during the construction of neural connections -- when the neural circuit is at work, for example, receiving olfactory sensations. Again, if it is working, there's more oxytocin in the brain, and when there's more oxytocin, more synapses are formed, and this again, increases the activity of circuits, and so on. As the authors of the study contend: "oxytocin drives the development and integration of new neurons in the adult brain, directly contributing to adaptability and circuit plasticity."

Does it mean that we already have in our hands a miracle medicine that will improve our "stiffening" with age network of nerve connections, one that can repair the declines experienced that result from disease or accidents? "Oxytocin is normally present in our brain, so if we know how to turn it on or off and mobilize it, we can help maintain healthy circuit connections by promoting the growth of underdeveloped connections or strengthening new ones," Prof. Arenkiel declares. Certainly, this hormone is a good candidate for such research. It has yet to be seen if it will promote the formation of new synapses to repair damaged tissue outside the olfactory bulb. While such studies are not yet underway, the oxytocin drug is registered for use in inducing labor contractions by intravenous or intramuscular administration.

However, there are serious risks to the idea of exploring oxytocin social engineering or the possibility of brain plasticity control on a massive scale. Overdoses of this drug or excessive sensitivity to it (or simultaneous disorders of the kidneys and adrenal glands) can even lead to life-threatening consequences. Water poisoning, as it is called, occurs when we have so much water in the body that our brain literally swells. Several other side effects may occur after administration of the drug, ranging from drowsiness and slurred speech to loss of consciousness.

The great mystery of brain plasticity, however, is beginning to be revealed before our eyes. And we wouldn't be human if we were not dreaming about resolving that mystery and learning to control the process by ourselves.

– Magdalena Kawalec-Segond

TVP WEEKLY. Editorial team and journalists

– Translated by Agnieszka Rakoczy Source:
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