Institute for Genetics, Faculty of Math. Nat. Sciences
In our increasingly aging society, neurodegenerative diseases are extremely relevant. On one hand, Prof. Dr. Matteo Bergami and his group investigate the cellular and molecular processes underlying acute brain injury and the ensuing inflammatory response. On the other hand, the team studies the mechanisms that regulate the regeneration of nerve cells with the hope of identifying cell-based replacement approaches towards repairing of damaged brain circuits.
Our research: Nerve cell dysfunction and its progression towards cell death is a primary cause of most aging-associated diseases in the brain. Research developed in recent years has explored new promising approaches for regenerating or replacing the damaged nerve cells. Together with his research group, Prof. Dr. Matteo Bergami investigates the mechanisms in the brain that regulate neurogenesis in the adult brain, in order to identify the fundamental principles that may allow nerve cell regeneration following brain damage from trauma and neuroinflammation, for example.
Our successes: For the most part, the adult brain lacks the capacity to regenerate functional brain cells. Neurodegenerative diseases, including brain injury, are characterized by a progressive and irreversible depletion of nerve cells that ultimately affect the integrity of brain circuits. Within this context, new strategies aimed to generate new functional neurons also require establishing the proper connectivity with pre-existing nerve cells. One success of Prof. Dr. Bergami’s research is the optimization of a technique that allows the mapping and investigation of how these new connections are formed, thus laying the groundwork for future therapeutic approaches to restore appropriate brain plasticity.
Our goals: Dr. Bergami and his working group focus on the molecular processes that allow the proper formation and connectivity establishment of new nerve cells in the adult brain. Their goal is to identify which mechanisms regulate neuronal regeneration and how these can be manipulated to reinstate functional neurogenesis in the diseased brain.
Our methods/techniques: Research in Dr. Bergami’s laboratory is performed using state-of-the-art imaging and molecular techniques. In particular, innovative tracing approaches permit the visualization and mapping of brain circuits under physiological conditions and during pathological states.
Figure 1: Time-lapse images showing a neuron before and after axon cut (red arrow). After 48 hours, one of the short neurites at the time of the axon transaction had grown into a new axon, which showed high p75NTR expression. Scale bar, 20 μm. (Zuccaro et al., 2013).
Figure 2: Virus-mediated monosynaptic tracing of neurons presynaptic to newborn neurons in the adult mouse hippocampus. The image shows a dentate gyrus newborn granule neuron at the age of 10 days (in yellow; co-labeled with a DsRed-encoding retrovirus and a GFP-encoding pseudotyped rabies-virus) being in direct contact with a first order presynaptic interneuron (in green; labeled with a GFP-encoding psudotyped rabies-virus only). Single stacks on the right show the emerging axon of the presynaptic neuron contacting the main dendritic shaft of the newborn neuron (arrowheads). (Deshpande et al., 2013).
Figure 3: In vivo labeling of the mitochondrial network in a cortical astrocyte (expressing mito-GFP, in green) being in direct contact with a cortical neuron (labeled in red). (Motori et al., 2013).