Category: Liza Olkhova

by Liza Olkhova

It is no longer surprising to hear that diet is just as important as lifestyle choices we make that determine our quality of life and longevity. With obesity levels rising globally, higher death rate and disability rise alongside this. An urgent need to raise awareness regarding imbalanced and damaging diet choices in children and adults is required in order to tackle this global problem and reduce its socio-economic impact.

More evidence comes to light to unequivocally support this notion from decades-long extensive study. A Lancet article published in April 2019 summarises a global study conducted worldwide in 195 countries from 1990 to 2017. The study assessed what risks are associated with lifestyle choices including suboptimal diet and tobacco smoking, alongside major diseases such as cancer.

It turns out that high blood pressure is the biggest killer with over 10 million deaths per year attributed to hypertonia. On the second place, however, is diet-related death with almost 9.5 million deaths per year. Surprisingly, tobacco smoking came third following diet.

Diet-related death is most commonly caused by cardiovascular disease, cancer and diabetes that have developed as a result of poor diet choices. For instance, high sodium content, consumption of red meat, processed food and sugar-packed beverages as well as low intake of health-boosting foods such as grains and fruits all attributed to the majority of death and disability cases.

How can we move away from this problem? Extreme changes to the diet in many countries have to be made on the national level, but of course, on the global level too. This includes education of children and public through campaigns, policy reforms to provide appropriate food labelling and price regulation, implementation of balanced diets in schools and universities, changes in taxation of various products (such as a recent ‘sugar tax’ in the UK on high-glucose drinks).

There is also evidence that substituting meat protein with plant-based protein source reduced the level of cardiovascular disease. Therefore, it could be worth letting people know about the healthy alternatives to their current diets instead of notifying them of what is unhealthy.

Read the Lancet article in full: https://doi.org/10.1016/S0140-6736(19)30041-8

by Liza Olkhova

Epigenetics – the study of how gene expression is altered without altering the gene sequence itself – may hold the key to how gene expression can be modified in the offspring of parents exposed to environmental factors such as severe stress, without offspring being exposed to the same factors. This can revolutionise the way we assess and deliver children healthcare

Gene expression regulation depends on various chemical modifications of the genetic code without alteration of the code letters themselves (mutations). Various chemical modifications of genes can either facilitate or hinder gene expression by altering the amount of protein synthesised from a gene.

So the question is, can these gene chemical tags be passed down to the next generations?

It has been shown that they are wiped out in egg and sperm cells, however small non-coding RNA (sncRNA) may be present in sperm and may affect the regulation of RNA levels in zygote and the developing embryo. Moreover, sncRNA molecules can be modulated by stress.

How could the trans-generational changes induced by stress be modelled in vivo? To answer this question, various mouse models were developed, in which mice were subject to stress. Surprisingly, changes in the RNA dynamics were passed on not only to the first generation of offspring, but also to further generations. These gene expression changes were accompanied by behavioural abnormalities, for example, more risk taking behaviour. Rodent behaviour was tested using a specially designed maze that assesses rodent exploratory behaviour.

The next aim is to explore how changes seen in sncRNA molecules in rodent models could be compared to changes in human physiology. For instance, a study involving analysing blood samples of soldiers before and after deployment showed increased levels of different types of sncRNA molecules with some of them correlating to post-traumatic stress disorder (PTSD).

Currently, the science is at the dawn of fully understanding epigenetic changes within human genome and how these changes could potentially be transmitted through to further generations. We have yet to witness more detailed and advanced human studies in order to gain a clearer perspective.

An ever-expanding number of frontiers of novel and revolutionary treatments is being explored by scientists in their efforts to combat Parkinson’s disease (PD).

A new trial, outcomes of which were published this month in Brain, tested the clinical efficacy of delivering a neurotrophic factor called GDNF directly into the brain area affected by the disease. When glial cell-derived neurotrophic factor (GDNF) was first identified along with the other factors, it was trialled in animal models of the disease and showed promising results. For instance, in rodent models of PD, which use a toxin that specifically targets dopaminergic cells that are lost in the course of disease, supplying GDNF factor was found to preserve those neurons previously exposed to the toxin. Neurotrophic factors essentially act to block any programmed cell death of neutrons and increase the number of signalling molecules that allow the cell to survive and proliferate. Their sole function seemed to be the much-anticipated key to reversing neuronal cell death and loss in PD.

Unfortunately, the subsequent randomised, double-blinded trial assessing the efficacy of administering GDNF directly into putamen did not find any statistically significant differences between treatment and placebo groups. Both groups showed a decrease in motor symptoms, potentially owing to the effect of placebo in such clinical trials, hindering clear understanding of the effects of the agent in question. However, almost half of all patients who had GDNF administered (compared to none from the placebo group) had a large decrease in their motor symptom score. Moreover, it was found through positron-emission tomography (PET) scanning that dopamine precursor uptake was significantly greater in the GDNF-treated patient group, indicating that dopaminergic cells in those patients are synthesising dopamine in higher amounts and hence are more actively functioning compared to the placebo-treated group. This indicates that this treatment and treatment with other neurotrophic factors, if administered using the same revolutionary delivery method, still hold promise if tested again in a wider setting of patients. The failure of this trial in part, in my opinion, could be explained by the relatively long duration of the disease (over 5 years since motor symptom onset). If this disease duration is decreased in subsequent trials, better results might be expected, as a greater number of neurons is lost the longer it has been since diagnosis. Therefore, if the factor is given at the earlier stages of the disorder, it may prevent the irreversible loss of vulnerable neurons that drive the progression of the disease.

by Liza Olkhova

Mediterranean diet, characterised by consumption of fish, olive oil, greens and grains, has been associated with healthier lifestyles and prolonged lifespan. Japanese diet has also been associated with longer lifespan, and the intake of fish and fish oils is prevalent in the Asian diet. Western diets, however, are largely based on meat products and a widespread use of butter, both of which are rich in saturated fats and cholesterol, which have been established to contribute to atherosclerosis. Atherosclerosis is a term for a pathological process that leads to a build-up of fat and inflammatory cells, eventually forming an atherosclerotic plaque within the walls of coronary arteries that supply the heart itself with oxygenated blood. If untreated, atherosclerotic plaques may cause heart attacks if the arteries’ lumen becomes too narrow to adequately supply the cardiomyocytes with oxygen and glucose.

What is the difference in oils and fats and how do we know which one is more likely to be beneficial? There is some evidence suggesting that increased intake of saturated fatty acids that only have single C-C bonds between the carbon atoms in their skeleton is not beneficial and might be damaging to cardiovascular health, whereas unsaturated fatty acids are considered “healthier” for the heart. Unsaturated means there is at least one or more double C=C bonds present within the fatty acid structure, called mono- and polyunsaturated fatty acids, respectively. But in biology nothing is ever quite so simple. A lot of fish oil supplements trials concluded that fish oil had no effect on protecting against cardiovascular diseases and scientists were trying to untangle whether some fatty acids and not the others could be beneficial.

An observational study conducted in Denmark and published this January in journal Stroke has ruled out that higher amounts of EPA are more beneficial than for example DHA in reduction of stroke associated with lower blood supply to the brain, called ischaemic stroke. Both of those fatty acids belong to the class of polyunsaturated fatty acids and are more commonly known by the name of omega-3s.

A clinical trial, REDUCE-IT, has compared EPA with placebo to identify if EPA may indeed reduce the rates of stroke in subjects. Indeed, they have found that the rate of strokes in the group of subjects that were taking high levels of purified EPA were decreased by almost a third compared to the control group taking placebo.

Therefore, it is important to address over-the-counter fish oil supplements and the proportions of different fatty acids that are within those oils and whether the level they are present at would cause an effect on reducing the risk of myocardial infarction and stroke. The balance and proportion of EPA to DHA may also determine this.

There are many other extremely important factors that determine the risk of cardiovascular diseases and must not be forgotten, including genetic predisposition, alcohol intake, smoking, unhealthy sleep patterns, age, lack of physical exercise, as well as diet. In the era of global obesity ‘pandemic’ we need to pay closer attention to our diet and make sure it is varied and balanced.

by Liza Olkhova

One of the first concepts stating that fermented foods might be beneficial to our health was proposed by a Russian scientist, Ilya Mechnikov, who discovered the endocytosis and pinocytosis functions of macrophages, where these immune cells engulf pathogens. He boldly claimed that consumption of fermented food may increase lifespan in his book titled The Prolongation of Life: Optimistic Studies.

We hear a lot on the news about the roles of prebiotics and probiotics in human health. Along with the rest of commensal microbiota, these bacterial species are well-understood to help with our digestion and shape our immunity. But can gut bacteria also influence our central nervous system function? In recent years, a boom in microbiome research provided us with new exciting insights into how trillions and trillions of microbes thriving inside the human organism may modulate its host’s health.

One of the first and very important studies that looked at the interplay between the microbes and their role in modulating stress hormones (released from adrenal glands when we get ill or stressed) was by Sudo and colleagues in 2004. They have shown that mice that were completely germfree released more of the stress hormone corticosterone (called ‘cortisol’ in humans) than their non-germfree counterparts (so-called ‘specific pathogen-free’). Interestingly, when germfree mice were given Bifidobacterium infantis, their stress hormone levels became less pronounced.

This study has ignited a chain reaction of many more animal studies that included behavioural work and human studies. Probiotic consumption was linked to improved mood, decreased depressive and anxiety scores in humans. The specific microbiome cluster (determined by the abundance of a particular type of bacteria in your GI tract) may not only dictate your emotional responses to what you perceive, but also predict your brain’s structural features as shown in a functional MRI study!

There has also been a clinical trial conducted by Akkasheh and others in patients with major depressive disorder that split patients into two groups: one was taking probiotic-containing pills and the other one was taking placebo. Patients and researchers were blinded to patients’ group allocation to prevent any bias influencing the results. It was discovered that patients supplemented with probiotics for 2 months had greater improvements in their symptoms compared with patients receiving placebo. What’s more, their C-reactive protein levels were also decreased, meaning they had decreased inflammation levels.

Microbiota can also produce or consume the major neurotransmitters – messengers of our brain, such as serotonin and dopamine. Clearly, there are a lot of unanswered questions about the microbiome and its links to major diseases, such as neurological disorders (for example, multiple sclerosis) and a lot more research is needed to show a more defined picture of the gut-brain axis.

Was Mechnikov right in his predictions made over a century ago and could a probiotic a day keep the doctor away?

Interested in learning more? Here are some useful links: https://www.ncbi.nlm.nih.gov/pubmed/15133062 https://www.ncbi.nlm.nih.gov/pubmed/28661940 https://doi.org/10.1016/j.brainres.2018.03.015 https://www.ncbi.nlm.nih.gov/pubmed/26706022

by Liza Olkhova 

Parkinson’s disease is the second most common disorder resulting in neuronal cell death following Alzheimer’s disease, and arises from the loss of dopaminergic cells in the midbrain. So far, treatment strategies have focused on replenishing the lost dopamine to improve patients’ motor symptoms such as resting tremor and muscle stiffness. These medications, however, may result in unpleasant side-effects.

Pluripotent stem cells are capable of differentiating into many different cell types, such as neurons, cardiac cells, etc. Generation of induced pluripotent stem cells (iPSCs) from adult cells, such as fibroblasts, and their subsequent differentiation into dopaminergic progenitor cells has been achieved at the Center for iPS Cell Research and Application (CiRA), Kyoto University. This technology would give a hope to not only compensate for a decreased dopamine neurotransmission, but to actually replenish the number of neurons that generate this neurotransmitter in the area of the brain affected in Parkinson’s.

Researchers at Kyoto University injected iPSCs-derived dopaminergic progenitor cells in the brains of macaques that were previously treated with a neurotoxin that causes Parkinson’s-like motor features. The grafted cells were not only able to survive, but to grow out its projections into other brain regions involved in movement. This led to amelioration of primate’s reduced motor functioning.

On the 1st of August 2018, a human Phase I/II trial was started in Japan to test the safety and efficacy of these cells in seven Parkinson’s disease patients by injecting the same brain region, called the putamen, with approximately five million iPSCs-derived dopaminergic progenitor cells (image). The cells will be injected into the putamen on both sides of the brain using stereotaxic equipment. Patients will be observed for two years during this trial and will be given immunosuppressant therapy in the case of transplant rejection.

The major concern surrounding such cell replacement therapies is a possibility of cells becoming tumorigenic; however, the original study reported no tumours formed in the macaque brain over the two-year time frame.

Cell replacement therapy could hold a promising potential to become a cure for Parkinson’s disease by directly restoring the dopaminergic neurons lost from the brains of patients, provided that clinical trials can prove the method’s safety and efficacy.

Please check out the following links for more information:
“‘Reprogrammed’ stem cells to be tested in people with Parkinson’s”
“Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model”

By Liza Olkhova

Anhedonia, or an inability to experience pleasure, is a prominent feature of anxiety and depression. It is a failure to seek rewards by avoiding anxiety-inducing activities or to modulate one’s behaviour according to rewards. Hence, susceptible individuals become less responsive to reward. Interestingly, it is possible to measure an individual’s response to receiving a reward, known as reward positivity, via electroencephalography (EEG) – a non-invasive method of measuring brain activity. An inverse relationship between reward positivity and depression symptoms has been reported by some studies.

The first study to look at linking reward positivity and patients’ responsiveness to either anti-depressants (in this case, selective serotonin reuptake inhibitors, or SSRIs) or cognitive behavioural therapy (CBT) was a publication by Burkhouse and colleagues. These two treatments are considered to be the gold-standard in depression: one pharmacological, which increases serotonin levels in synapses and is believed to elevate mood, and one, CBT, a method of talk therapy. However, many patients with depression do not improve their symptoms following either of these therapies and often develop unpleasant side-effects with SSRIs.

Authors of the study asked the simple question of whether the baseline reward positivity (measured before the treatment onset) would predict the symptom lessening following the 12-week treatment with either SSRIs or the CBT. The second question was whether the difference between post- and pre-treatment reward positivity would correlate to a reduction in depressive symptoms. To measure reward positivity, participants were asked to choose one out of two doors in the computer task, a guessing game in which you either gain or lose money depending on the decision made.

The results have established the positive relationship between reward positivity and improvement of depressive symptoms. Reward positivity seems to also emerge as an objective neurophysiological predictor of responsiveness to the SSRI treatment, but not to CBT, using EEG. Authors have found that an attenuated reward positivity signal predicts reduction of symptoms in patients with depression.

This EEG method has promising potential as an objective predictor of anti-depressant therapy and a marker of treatment efficacy. Moreover, it is readily available in clinical settings and has advantages over the subjective depression rating scales that are used in the majority of clinical trials, but are highly subject to placebo effects.

Please head over to https://www.psychiatrist.com/JCP/article/Pages/2018/v79/17m11836.aspx to read the original study.

By Liza Olkhova

What is the definition of the classification term ‘species’? In biology class we usually learn that members of the same species are capable of breeding and producing fertile offspring. However, with recent discoveries of the new species within our genus Homo and some genomic revelations about our own species Homo sapiens sapiens, this definition suddenly becomes a blurred one.

This story is ultimately about caves, bones and stretches of genetic code, which can be aligned and compared between different species to give us an idea of how closely related they are and even an estimation of the point in time at which they diverged.

Most of the Neanderthal genome was obtained from individuals found in the Vindija Cave, Croatia, and it shows that present day humans of European descent carry approximately 1-4% of the Neanderthal genome. It means that our species was successful at interbreeding with other species of the Homo genus.

In 2010, a major finding was made within one of the caves located in the Altai Mountains, southern Siberia. Denisova Cave had ancient secrets buried inside, including the remains of another yet-undescribed hominin: a tooth and a finger bone, from which DNA was extracted. At this point, a pattern started to emerge, and decoding the DNA demonstrated that Homo sapiens had also bred with Denisovans. However, stretches of Denisovan genetic information can also be found in modern-day Melanesian populations, for example, in Papua New Guinea. This poses the intriguing question of how Denisovans or the Homo sapiens who interbred with them might have migrated to these regions from Siberia.

An evolutionary tree according to Darwin and most people’s understanding of evolution is represented by clear-cut linear branches with distinct separation. As with the majority of biological processes and events, however, it is a lot more complex: we are now able to see how these branches intertwine, giving us a much messier, but complete, depiction of evolution of our genus. Blue arrows on this tree show interbreeding and the moment in time where it was most likely to occur. This representation shows that Denisovans and Neanderthal groups are more closely related to each other than either of them to Homo sapiens.

To complicate matters even further, geneticists that have looked at over 5000 genomes collected from across the globe have found that some of the ancient chunks of DNA do not match Neanderthal nor Denisovan DNA sequences, hinting at the existence of another yet unknown ghostly hominin species.

As both Neanderthals and Denisovans are extinct, we are the only modern human species remaining. However, our species’ capacity to interbreed with both means that we still carry their DNA within us .

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Post was inspired by a book called A Brief History of Everyone Who Ever Lived written by Adam Rutherford. If you would like to find out more head over to:

https://www.nature.com/articles/nature09710
https://www.nature.com/news/2011/110809/full/476136a.html
https://www.nature.com/news/modern-human-genomes-reveal-our-inner-neanderthal-1.14615
https://www.newscientist.com/article/2163910-our-ancestors-mated-with-the-mystery-denisovan-people-twice/
https://www.newscientist.com/article/mg21128323-200-the-vast-asian-realm-of-the-lost-humans/
https://www.newscientist.com/article/mg21128254-000-stone-age-toe-could-redraw-human-family-tree/

By Liza Olkhova

When you are learning a foreign language, you are bound to come across unknown  words or even expressions in text or speech. From my personal experience, it acts as a great learning tool, as you are sometimes able to assign a meaning to the unknown word based on the context. While reading a text it is not surprising that people usually predict the upcoming words based on their fluency and past experiences, aiding the cognitive processing.

Bilingualism is often considered to be advantageous to cognitive abilities. It is also believed that bilinguals’ reading skills are different to those of monolinguals, however a study published in Cognition has challenged this notion. The study sought to compare both monolingual and bilingual students recruited from Pennsylvania State University, USA, and has demonstrated that bilinguals are able to exploit strategies to predict upcoming words judging from the sentence context in a similar way when compared to their monolingual peers. For example, a sentence that was used in the study ‘After their meal, they forgot to leave a tip for the waitress’. In this sentence the predicted word would be ‘tip’, but the unexpected word used by researchers would be ‘ten’.  Zirnstein and others used electroencephalography technique (EEG) to measure brain electrical changes picked up by multiple electrodes sitting on the surface of the skull. Scientists were able to link some of the changes to the brain’s response to prediction error. The area that appeared most active when the word was different from the one predicted by study participants was the frontal cortex, crucial for decision making and other executive functions.

The results depended on language fluency as well as the inhibitory control of bilinguals. This means people who can speak at least two languages need to engage in dynamic shifts in executive functions to control both languages by constantly switching between activating one and suppressing another. Bilinguals may either disengage from one language when it may interfere with the other or activate it to aid in another.  In my opinion as a person fluent in Russian and English languages, this is also true. If I come across a scientific text written in Russian it poses a more demanding task to read compared to when it is written in English, probably because I am much more immersed in scientific content entirely written in English. In the former example, activation of my second language, English, when reading a word ‘mitochondrion’ (‘митохондрия’) in Russian as it is a similar word achieves cross-language support. On the contrary, by inhibiting English language when reading Russian for ‘cerebellum’ (‘мозжечок’) as it an entirely different word prevents cross-language interference.

Zirnstein M, van Hell J, Kroll J. Cognitive control ability mediates prediction costs in monolinguals and bilinguals. Cognition. 2018;176:87-106.

If you would like to find out more about the original study, head to https://doi.org/10.1016/j.cognition.2018.03.001.