DZNE neuroscientist receives grant to study link between neurodegenerative diseases and mental health

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Neurodegenerative diseases such as Alzheimer’s and Parkinson’s can be associated with depression and anxiety. Dr. Sabine Crabbe, a neuroscientist at DZNE’s forest site, is receiving $1.2 million from the Chan Zuckerberg Initiative to understand the mechanisms involved in the onset of these syndromes. To this end, he aims to examine the function of the brain’s “emotion center” using new methods to examine single cell function in experimental mouse models. The study will run for four years and aims to pave the way for better treatments in people affected by the condition.

Psychiatric disorders are shared by multiple neurogenerative diseases, affecting approximately 60 to 70 percent of patients. Anxiety and depression are especially common. These problems affect patients’ well-being and severely reduce their quality of life. Notably, they can occur years before the onset of memory problems or movement disorders. In other words, long before Alzheimer’s, Parkinson’s or any other neuroregenerative disease is diagnosed. This suggests that diagnosis must have primary biological causes in addition to psychological burden.”

Dr. Sabine Crabbe, DZNE’s forest site neuroscientist

With the funded project, the neuroscientist, who heads a research group at DZNE’s forest site, aims to contribute to a better understanding of the underlying phenomenon. He says: “I want to not only understand neuronal processes, but also to find approaches to better treat mental disorders associated with neurodegenerative diseases.”

Emotional center spotlight

On a microscopic level, diseases like Alzheimer’s and Parkinson’s have one thing in particular in common that may be related to emotional problems: protein deposits in the amygdala, the brain region specifically involved in emotion regulation. Hence it is sometimes called the “emotion center” of the brain. “My hypothesis is that these proteins disrupt the neuronal networks within the amygdala and cause psychiatric phenotypes. In this regard, my research focuses on the amygdala and specifically on the psychiatric symptoms of neurodegeneration. We want to find out how these abnormal proteins affect the amygdala. To date , their effects have mainly been investigated in other regions of the brain.”

Behavioral experiments

The research project is scheduled to run for four years and is highly complex, as it combines extensive behavioral experiments with state-of-the-art microscopy methods. The focus of the study will be on mice with protein deposits in the amygdala that occur in Alzheimer’s or Parkinson’s disease. In technical terms, these are referred to as “mouse models”. “The amygdala has the same structure and function in all mammals. So we can learn a lot about human brain processes from observing mice,” says Crabbe. “For example, we will analyze how mice explore an unfamiliar environment and whether the animals are bold or rather reserved. From this, we can make conclusions about their mental state. We will use a full range of standardized test protocols for this and similar experiments. And we will We can do this through the different stages of the disease to observe the changes associated with its progression.”

Cellular precision

Behavioral experiments are complemented by microscopic measurements of the activity of neural networks and even individual cells. For this, Krabbe and his team are using tiny microscopes weighing less than two grams. “A rat can wear such a device on its head without any problem, while it is freely moving around. We record what the animal is doing at a given time and what is happening simultaneously in the amygdala. The behavior can be linked to neuronal activity, and the progression of the disease. Changes can be registered,” explains Crabbe. “Also, we have techniques to identify different cell types in the amygdala. This allows us to determine, for example, whether the disease affects certain types of neurons more than others.”

Searching for common processes

Forest scientists hypothesize that different neurodegenerative diseases affect the amygdala in the same way. “This would explain why similar psychiatric symptoms are observed in disorders as different as Alzheimer’s and Parkinson’s. In light of this, we are investigating related mouse models,” Krabbe said. “So I hope to find common mechanisms in the pathology within the amygdala. This will probably enable a joint therapeutic approach. Many people with neurodegeneration could benefit from this.”

International network

Selection of the Chan Zuckerberg Initiative gave Sabine Crabbe the opportunity to interact with numerous experts. This is an interesting prospect for the 39-year-old neuroscientist: “Together with my team, I am part of an international community, the Neurodegeneration Challenge Network, which includes people from different disciplines and expertise. It consists of both junior researchers new to the field. And established scientists who have been dealing with neurodegeneration for a long time. Working. You can take a lot of tips and advice from such a community. On the other hand, I look forward to contributing my experience with our very specific methodology and experimental. Data we will generate.”

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