Neurodegenerative diseases like Alzheimer’s and Parkinson’s can be associated to depression and anxiety. Dr. Sabine Krabbe, a neuroscientist at DZNE’s Bonn site, is receiving 1.2 million US dollars from the Chan Zuckerberg Initiative to understand the mechanisms involved in the onset of these syndromes. To this end, she aims to examine the function of the brain’s “emotion center” using new methodologies to examine the function of single cells in experimental mouse models. The study will run for four years and intends to pave the way for better treatments in humans affected by these conditions.

Psychiatric disorders are shared by multiple neurogenerative diseases, affecting around 60 to 70 percent of patients. Anxiety and depression are particularly common. These issues affect the patients’ well-being and severely reduce their quality of life. Remarkably, they can occur years before the onset of memory problems or movement disturbances. In other words, long before Alzheimer’s, Parkinson’s or another neurogenerative disease is diagnosed. This indicates that there must be early biological causes in addition to the mental burden later caused by diagnosis.”

Dr. Sabine Krabbe, neuroscientist at DZNE’s Bonn site

With the funded project, the neuroscientist, who heads a research group at DZNE’s Bonn site, aims to contribute to a better understanding of the underlying phenomena. She says: “I not only want to understand the neuronal processes, but also find approaches so that psychiatric disorders associated with neurodegenerative diseases can be treated better.”

Spotlight on the emotion center

At a microscopic level, diseases such as Alzheimer’s and Parkinson’s have especially one thing in common that might be related to psychiatric problems: protein deposits in the amygdala, the brain region that is particularly involved in controlling emotions. Hence it is sometimes called the brain’s “emotion center”. “My assumption is that these proteins disrupt the neuronal networks within the amygdala and that this causes the psychiatric phenotypes. In this respect, my research focuses on the amygdala and specifically on psychiatric symptoms in neurodegeneration. We want to find out how these abnormal proteins affect the amygdala. To date, their influence has mainly been investigated in other brain areas.”

Behavioral experiments

The research project is scheduled to run for four years and is extremely complex, as it combines extensive behavioral experiments with sophisticated microscopy methods. The focus of the studies will be on mice with protein deposits in the amygdala similar to those occuring in Alzheimer’s or Parkinson’s disease. In technical jargon, these are referred to as “mouse models”. “The amygdala has a similar structure and function in all mammals. We can therefore learn a lot about processes in the human brain from observing mice,” says Krabbe. “For example, we will analyse how mice explore an unknown environment and whether the animals are courageous or rather reserved. From this, we can draw conclusions about their emotional state. We will use a whole range of standardized test protocols for these and similar experiments. And we can do this through different phases of disease to observe changes associated with its progression.”

Cellular precision

The behavioral experiments are complemented by microscopic measurements of the activity of neural networks and even individual cells. For this, Krabbe and her team are using miniature microscopes weighing less than two grams. “A mouse can wear such a device on its head without any problems, while it moves around freely. We record what the animal is doing at a particular time and what is happening simultaneously in the amygdala. Behavior can thereby be linked to neuronal activity, and changes over the progression of the disease can be registered,” explains Krabbe. “Furthermore, we have techniques to identify different cell types in the amygdala. This allows us to determine, for example, whether the disease affects some types of neurons more than others.”

Searching for common mechanisms

The Bonn scientist presumes that different neurodegenerative diseases influence the amygdala in a similar 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 corresponding mouse models,” says Krabbe. “I therefore hope to find common mechanisms in the pathology within the amygdala. This would probably enable a joint therapeutic approach. Many people with neurodegeneration could benefit from this.”

International network

The selection by the Chan Zuckerberg Initiative also offers Sabine Krabbe the opportunity to interact with numerous experts. This is an appealing prospect for the 39 year-old neuroscientist: “Together with my team, I am part of an international community, the Neurodegeneration Challenge Network that includes individuals from diverse disciplines and expertise. It consists of both junior researchers new to the field and established scientists who have been working on neurodegeneration for a long time. You can pick up a lot of tips and advice from such a community. On the other hand, I am looking forward to contributing my experience with our very specific methodology and the experimental data we will generate.”