Researchers who work on neurodegenerative disorders like Parkinson’s or Alzheimer’s disease need to access diseased human brain cells very frequently. In that process, they create diseased human brain cells from human pluripotent stem cells in the lab. However, the main problem in the procedure is, they cannot regenerate enough diseased neurons to study the diseases more closely. This is the reason that the diseases still cannot be detected at an early stage or we don’t have any proper drug to delay the occurrence of the diseases.

To overcome the issue, scientists would need a resource to regenerate human brain cells in bulk. To address it, a team of researchers from Lund University built a new technique to effectively regenerate brain cells in bulk from patients, suffering from neurodegenerative diseases like Huntington’s, Parkinson’s, and Alzheimer’s diseases. Dr. Malin Parmar is the senior author of the study, which is published in EMBO Molecular Medicine.

Earlier studies showed that reprogramming the cells back to the pluripotent stem cell state wipes out the aging effects in the cells. So, the team employed an alternative method to create the neurons. The approach involved turning the human skin cells into brain cells. They did not reprogram the skin cells to the pluripotent stem cells in the first place. The method is called “direct conversion”, which is considered to be an efficient shortcut to regenerate mature brain cells in a dish. Once the direct conversion was applied, the aging signs remained intact, which resulted in an aging brain.

Parmar explained, “Primarily, we inhibited a protein, REST, involved in establishing identity in cells that are not nerve cells. After limiting this protein’s impact in the cells during the conversion process, we’ve seen completely different results.” This technique also helped them to study aging brain cells at different levels of the diseases, as aging is one of the main risk factors in these diseases.

The method was developed entirely to regenerate human brain cells in large quantities, so the scientists have access to a sufficient number of diseases brain cells to conduct their researches. However, early detection also plays a significant role in treating diseases. For this reason, as well, the scientists wanted a technique that offers a way to test new drugs to treat or delay the symptoms of these neurodegenerative diseases.

The team also created two proteins, Ascl1 and Brn2. These proteins are important to regenerate brain cells. Parmar said, “We’ve been playing around with changing the dosage of the other components in the previous method, which also proved effective. Overall, the efficiency is remarkable. We can now generate almost unlimited amounts of neurons from one skin biopsy.”

Dr. Johan Jakobsson, the co-author of the study said, “This takes us one step closer to reality, as we can now look inside the human neurons and see what goes on inside the cell in these diseases. If all goes well, this could fundamentally change the field of research, as it helps us better understand the real mechanisms of the disease. We believe that many laboratories around the world would like to start testing on stem cells to get closer to the diseases.”

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Modern medical science has proved many old notions wrong. Our belief that the adult brain cannot grow new neurons, is one of them. Researchers now have proved that the stem cells, present in our brains can generate new neurons and the use of Prozac or any other anti-depressant drug may help in neurogenesis (the growth of new nervous tissue). The discovery has also led to new insights like how an adult brain functions and what it might take to treat brain-related conditions such as depression.

RIKEN institute researchers have developed a new and non-invasive technique to detect the generation of new neurons from the stem cells in the brain. Measuring new brain cells non-invasively was, however, a challenging process. Both the Magnetic resonance imaging (MRI) and the positron emission tomography (PET) scanning are risky and difficult to conduct and the signals, received are also non-definitive.  However, the RIKEN team has come up with the solution by adding proteins in the PET signals.

They used a clinically available drug in the PET process to block the transporter proteins. And the result was a clear neurogenesis signal. Yosky Kataoka, the lead of the team behind the study said, “This is a very interesting finding because it has been a long-time dream to find a noninvasive test that can give objective evidence of depression and simultaneously show whether drugs are working in a given patient.”

The study was conducted on rats. The PET technique involves injecting a small amount of a radioactive tracer to stick to a targeted molecule in tissues, so that the scientists can scan and track the gamma rays, emitting from that region. The rats were divided into two groups. Over the period of a month, the first group was given a stress hormone, corticosterone in order to induce a depression-like behavior. And the second group received both the corticosterone and the antidepressant drug, Prozac.

After they scanned the brains of the animals, they found out that the radioactivity was prominent enough to tell apart the differences between the damaging effects of the stress hormone and healing effects of the antidepressant. The PET scan signal helped the researchers to detect a decrease in neurogenesis in the first group of rats, who received only the stress hormone, whereas they found a recovery in neurogenesis in the second group of rats, who were given both the hormone and the drug.

The enhanced PET imaging method not only proved that the adult brain neurogenesis can be detected and measured, but it is also able to track the dynamic changes in the rate of the progress due to the antidepressants. The results confirmed that the first group, treated with the stress hormone, corticosterone, showed about 45% fewer newborn brain cells, compared to the untreated animals. However, the second group, who received both corticosterone and Prozac, displayed no such result.

Even though the experiment was entirely done on animals, the team is now eager to apply this non-invasive imaging technique to detect and measure depression in humans. Kataoka confirmed, “Since it is known that these same brain regions are involved in depression in the human brain, we would like to try this technique in the clinic and see whether it turns out to be effective in humans as well.”

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Ageing is a part and parcel of life, but as our body ages, our brains age too. Just like an ageing body can be riddled with diseases and illnesses like arthritis, cataracts, cardiovascular disease and osteoporosis, an ageing brain too can be afflicted with sickness. The age-associated diseases that affect the brain are often clustered under the umbrella term of ‘neurodegeneration’. Diseases like Huntington’s, Alzheimer’s and Parkinson’s are some of the better-known disorders that fall under this terminology.

Let us first understand what the term ‘neurodegeneration’ actually encompasses.  The Oxford Dictionary defines neurodegeneration as the “Degeneration of the nervous system, especially of neurones in the brain”. According to the EU Joint Programme – Neurodegenerative Disease Research (JPND), the nervous system of the human body comprises of neurones. In case they suffer damage, they do not possess the ability to repair, replace or reproduce themselves. This inability results in neurodegenerative diseases.

Previously, neurodegenerative diseases were believed to be incurable. However, with the gigantic steps towards advancement that medical science has taken in the recent years, scientists have been able to devise procedures that help in assisting individuals suffering from neurodegenerative disease. Stem cell therapy is among these advanced procedures that have recently shown positive results.

Stem cells are mother or master cells that have the ability to differentiate into other types of specialized cells through the process of mitosis. They can repair internal tissue damage by developing into a cell with a specialized function like a blood cell or brain cell.  They also possess the ability to renew themselves.

Utilizing stem cells to treat medical disorders and diseases is known as stem cell therapy. Transplantation of stem cells is the most common procedure used in stem cell therapy. In cases of brain degeneration, stem cells are transplanted into the patient. These stem cells then become progenitor cells that work within the brain to maintain the neurone functions. Research has been conducted on animal models for diseases like Amyotrophic lateral sclerosis, Parkinson’s, and multiple sclerosis, which have provided optimistic outcomes.

In a symposium organized by EuroStemCell, Magdalena Götz, Ph.D., Helmholtz Zentrum München, spoke about the radial glial cells which are present in the neural stem cells and described them as “they look like glia, they smell like glia but they are actually the neural stem cells.” She further explained the development of brain cells and the possibility of guiding neural stem cells to locate and repair the injury site inside the brain, while also regenerating neurones.

Stem cell research is the future of neurology. With several clinical studies being conducted year after year, the use of stem cell therapy in treating neurological disorders is constantly expanding. In India, the guidelines established by the Indian Council for Medical Research (ICMR) for conducting clinical studies have been revolutionized leading to extensive research being done in the field of stem cell therapy.

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