What makes a person capable of making decisions? A complex cognitive mechanism, implicated in our behavior but also in some pathologies, of which in recent years we know more and more at the level of brain areas. That is, research has made it possible to identify which parts of the brain are activated when we think and decide. However, little is known about the cells and molecules involved in the decision-making process. An important piece to this puzzle has now been added by a team of researchers from the Neuroimmunology Unit of the IRCCS San Raffaele Hospital who have identified a population of brain cells – periventricular stem cells – and a protein they secrete – insulin-like growth factor binding protein-like 1 (IGFBPL1) – the lack of which makes you less able to decide, in other words makes you more indecisive.
The study, published in Nature Communication, conducted on an experimental model, also shows a correlation between people with multiple sclerosis, who show cognitive disorders such as the difficulty in processing information, and the presence of brain lesions due to the disease precisely in the area ‘ periventricular’ where IGFBPL1-producing stem cells are present. “This discovery adds a piece to our understanding of how our thinking in general and our ability to decide in particular works at a biological level, and suggests once again that some processes that may seem strangely complex to us are regulated by however identifiable molecular mechanisms. We hope to be able to use this knowledge in the near future to develop specific therapeutic interventions for people with neurodegenerative diseases and cognitive disorders”, explains Gianvito Martino, head of the research team, neurologist, neuroscientist and scientific director of the IRCCS.
The work was possible thanks to the support of the Progressive MS Alliance (BRAVEinMS) and the Italian Multiple Sclerosis Foundation (FISM). “Cognitive impairments are a real priority for people with neurodegenerative diseases such as multiple sclerosis. Knowing the mechanisms underlying these disorders, making them increasingly scientifically measurable (PROMS), as well as listening to their experience of the disease over time is necessary in order to be able to translate this important discovery into personalized therapeutic interventions” adds Paola Zaratin, AISM scientific research director /FISM.
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I study
Researchers, studying periventricular stem cells – cells located around the cerebral ventricles in which the cerebrospinal fluid that supplies and nourishes the brain flows – have discovered that they secrete a protein – IGFBPL1 – whose role is to carry out a trophic action on some cells located in a deep brain area called the striatum. In this area, the trophic effect of Igfbpl1 is exercised in favor of some cells, defined as fast-spiking interneurons, which are essential for cognitive processes because they are capable of inhibiting electrical impulses coming from any brain area. In doing so, these cells are capable of filtering ‘electric’ messages by passing only those destined to become precisely a decision, whether right or wrong.
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The researchers demonstrated that by genetically knocking out the periventricular stem cells and/or the IGFBPL1 protein, the modified mice were left undecided. In fact, deprived of cells or protein, they have shown, during behavioral tests, that they are unable to adequately regulate the impulses aimed at facilitating or inhibiting a certain behaviour, while maintaining the learning and memorization capacity intact.
Erica Butti, researcher of the Neuroimmunology Unit explains: “This work allows us to know a little more about the function of stem cells in physiological conditions. In fact, the lack of these cells in the brain of our experimental model causes morphological and functional alterations of the neurons present in the striatum, which in turn lead to the creation of a cognitive deficit. Stem cells secrete many proteins and through RNA sequencing experiments we found the protein, precisely, called IGFBPL1. The lack of this protein no longer allows stem cells to be so efficient in controlling the neurons of the striatum, causing precisely those cognitive deficits mentioned above. The discovery that these cells can also be involved in cognitive/decision-making processes is a contribution to trying to better understand what happens in neurodegenerative diseases that determine important cognitive deficits”.
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The development of neurocognitive knowledge
The anatomical definition of the various (macro) brain areas in which our cognitive processes take place, begun as early as the 19th century by the Pavia school and by personalities such as Paul Broca, has already reached an advanced level of detail. In the last century the development of micro and macro (neuro)images and of the so-called ‘in vivo’, ‘real-time’ neurophysiology made it possible to define in great detail some circuits composed of brain nerve cells, called circuits or neural networks, which, for example, underlie attention or mnemonic processes, guide the planning of actions and allow sensations or emotions to be felt.
Among the various processes of thinking, that of decision remains among the most interesting and least known. The interest arises above all from the fact that they are circuits involved in many processes that also have repercussions in areas other than the pre-eminent ones of the life sciences, not least the interest of ‘behavioral’ economics as well as psychology and pedagogy. In recent years it has been defined which are the most involved and important brain areas capable of guaranteeing us this mental process; on the other hand, the biomolecular context is little known since we do not yet know which are the cells and molecules that allow us to make a decision.
“The research in question has therefore added relevant information to the map being defined and which reports the data relating to the code that underlies our thinking in general, and our decisions in particular”, concludes Martino.
