Share Your Science (II)

In this new post about scientific dissemination, the biotechnologist and CENL member Blanca Torroba talks about neuroscience and Alzheimer’s disease

Blanca Torroba Balmori

Hi! My name is Blanca Torroba Balmori and I am a biotechnologist. During my studies I got very interested in Neuroscience, a field as attractive as complex, and I have been working on it since then.

Before coming to live to the Netherlands, I worked as postdoctoral researcher at the University of Oxford in a project founded by a spin-off company who wanted find a compound to treat Alzheimer´s disease through a new approach: via stimulation of the adult neurogenesis. It is a fascinating topic and I would like to share some curiosities about it with you in this blog.

Alzheimer´s disease was named after Alois Alzheimer, one of the first scientists to describe it at the beginning of the 20th century. Alzheimer observed macroscopic changes in the brain of some people with dementia showing severe memory loss and disorders of speech among other symptoms. Nowadays, we know that these changes in the brain are caused by the accumulation of two types of protein aggregates, beta-amyloid and Tau, clocking up in deposits and altering the sensitive processes that occur within a neuron. It is similar to adding minuscule rocks to the mechanism of a Swiss watch.

Accumulation of these “pebbles” inside the brain during the disease usually starts in an area called “hippocampus” (named like that because of its resemblance to a sea horse), very important for memory and mood control. As a result of this, the neurons affected start to die and some brain functions are disrupted, such as the memory. Unfortunately, this cell death keeps progressing into other brain regions like a slow blast wave and that´s why this disease is called neurodegenerative and symptoms  increase with time.

Reports analyzing worldwide data estimate that more than 50 million people around the world are affected by Alzheimer´s disease. And this number is expected to go up over the years due to an increment in the life expectancy. Therefore, efforts are being made in this race against time to better understand its causes and to find effective ways to treat it.

There are three main aspects to consider when dealing with such a complex disease: to eliminate the cause, to halt neuronal death and to regenerate the tissue to recover the lost functions. This last point is the link to the idea that, perhaps, stimulation of the adult neurogenesis could be used as therapeutic approach. But let´s take a break here since you might be wondering what´s the so called adult neurogenesis and a proper introduction is, by all means, needed.

Neurogenesis means generation of new neurons. The Nobel Prize Santiago Ramon y Cajal believed that the adult brain was fixed and unchanging and so the neurons could die, but not being generated. And this was the dogma for many years.

Nonetheless, later studies in different animal species (fishes, birds, rats, etc.) and some in humans showed the opposite: new neurons can be generated! This is an interesting example of how the knowledge is built. First, a hypothesis (explanation of an observed phenomenon) is proposed based on the available information in a specific moment (beginning of the 20th Century in this example). But later on, when technology and new studies allow us to have more accurate information, then the old hypothesis is corrected and improved (50 years later in this case).

In spite of what we know about the brain of many other animal species, however, the existence of adult neurogenesis in humans is still under debate, with scientists in favour and against it. The reason behind it lies in the complexity of observing what happens within the human brain. And some of the main studies supporting adult neurogenesis are very difficult to replicate.

One of those studies was published in 2013 by Jonás Frisen´s lab, at Karolinska Institute in Stockholm. Frisén collected brains from deceased people who had lived in areas with radioactive dust released by nuclear bomb tests above ground in the EEUU during the Cold War. Among the isotopes thrown out by the bomb there was carbon-14, extremely rare, which ended up accumulated in plants. People of different ages fed on those plants and incorporated the carbon-14 in their newly generated cells, such as those on the skin, hair, etc. When scientists studied their brains they observed that some of their neurons also contained carbon-14, even if they were adults when they ate those plants, concluding that humans can produce new neurons during their lives. But not in the whole brain! Those new neurons only appear in the hippocampus and they seem to be very important for memory processes.

For that reason, a group of scientists of the University of Oxford decided set out on a project to find a drug that could stimulate the production of new neurons in the hippocampus and, this way, regenerate memory functions in Alzheimer´s disease. This is a challenging quest, but there are some options available to tackle it. One of them, used in this project, was to take advantage of the abundant existing knowledge about adult neurogenesis in mice. Using this animal model it is possible to reproduce the adult neurogenesis in vitro, isolating cells from mouse brains to test compounds before moving into human studies.

The search for this drug still continues, as well as the race to understand if the brain can regenerated. As curiosity, in case you wonder how those mysterious cells look like, you can take a look at the two images below showing the in vitro cultures (left image) and the hippocampus of a mouse (right image).

 

 
Cell cultures with new-born neurons (in red) and astrocytes (support cells, in white), the blue dots stain the nuclei of those cells.
Mouse dentate gyrus, the region of the hippocampus where the adult new neurons are born (stained in white and green).
If you would like to know more about this fascinating topic, feel free to check these reviews about it:

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