The results of Dr. Dasfne Lee’s work may have implications for the understanding and treatment of neurodegenerative diseases and other brain pathologies. Her research on cerebral energy metabolism would shed new light.
The brain is an organ that is still not fully understood, especially in contexts in which its functioning is altered; for example, with aging or in the presence of diseases and disorders. Dasfne Lee Liu, Ph.D. in Biological Sciences, an academic at the Faculty of Medicine and Science of the USSseeks to determine how the metabolic relationship between two types of cells in the brain, neurons and astrocytes, fails when brain function is altered. That is, what fails in their joint work in relation to obtaining and using energy.
“The brain spends between 20 and 25% of the energy that the body spends, despite the fact that it only represents 2% of the body size. Therefore, the energy metabolism in this organ is crucialexplains Dr. Lee.
“We intend to study how two cells work in the brain: neurons, which we all know, and a cell that has historically been given the role of support, called an astrocyte, but in reality, both cells work together, and without the astrocyte. , the neuron could not function. It plays a very important role in the brain, especially at the level of energy metabolism”.
For this, the academic performs laboratory work, as well as computational modeling, to discover which enzymes and/or transporters in the metabolic network that make up the astrocyte and neuron they are affected in contexts of brain dysfunction, such as aging, where our cognitive ability declines with age.
Research advances
“First, we used two computational modeling approaches that allowed us to identify the most important genes for the functioning of the metabolic network between the neuron and the astrocyte. We identify them by simulating what happens when each one of them is eliminated, with the global operation of the entire network. We then identified which of these genes are deregulated during aging in these two cells, giving us candidate genes that may be responsible for the cognitive decline that occurs as we age, or that increase the risk of neurodegenerative diseases. The next step will be to modulate these genes in neurons and astrocytes in laboratory experiments.”
Dr. Lee adds that “This is important because in many types of conditions or pathologies, ranging from the development of schizophrenia or epilepsy, to autism.there is a dysfunction in energy metabolism while they are developing, but we still don’t know how it happens.”
Another particular aspect of Dr. Lee’s line of research is the study of metabolism in the context of brain aging and its relationship with energy levels and life expectancy.
“This is a side project that we worked on a lot during the pandemic because we couldn’t do experiments in the lab. But as we were generating results, with this integrative computational approach that hadn’t been done before, we found some very interesting things, and we realized that this approach would be very valuable for the future. For example, the only intervention known to prolong life expectancy is caloric restriction (eating 60-70% of normal daily calories). When we do this, ketone bodies increase, and in our analyses, we found genes related to ketone body metabolism that are deregulated during aging in astrocytes and neurons. This is important because we don’t yet know how ketone bodies work to increase lifespan, and these genes may shed light on the mechanisms through which this occurs.”
The academic says that she began to study energy metabolism through spinal cord regeneration in an African frog called Xenopus laevis, which has the ability to regenerate its spinal cord while it is in its tadpole stage, an ability that is lost once the frog reaches adulthood.
“We realized that energy metabolism plays a crucial role in the regeneration of the spinal cord, and we have been working on this line of research for several years. However, the study of brain metabolism is relatively new, and we have only been working on it for a few years, but we have already obtained promising results.”
In short, Professor Dasfne Lee’s research aims to help clarify how the brain works at a metabolic level, and how it can be affected in different contexts. The results of their work may have implications for the understanding and treatment of neurodegenerative diseases and other brain pathologies.
