Leuven, Belgium − Every year, one million Europeans are confronted with potentially irreparable brain or spinal cord injuries resulting from traffic accidents. Because the nerves in a damaged spinal cord cannot, or cannot fully, be repaired, the patient remains (partially) paralyzed. Now, VIB scientists connected to the K.U.Leuven have become the first to successfully develop a simple model that enables the study of injured brain tissue. The researchers have perfected a technique for keeping the cultured brain of a fruit fly alive and healthy for a longer period of time. With the aid of microsurgery, this new technique enables scientists to inflict injury on certain nerve bundles for research purposes. By means of this new fruit fly model, the researchers have already succeeded in showing that the activation of a particular signaling pathway (JNK) induces the regeneration of axons. This research offers positive perspectives for patients with nerve injuries that have been irreversible up to now.
Drosophila as model organism
The Drosophila melanogaster fruit fly is an important, low-cost model organism with a 60% genetic similarity to humans. The fruit fly is playing a significant role in the elucidation of various neurological processes (such as the functioning of our memory and our sense of smell) as well as in the study of certain neurodegenerative diseases (such as Alzheimer's disease). Until recently, scientists could only use model organisms belonging to the vertebrates (e.g., the mouse) to study injuries to the nervous system and the possibility of regenerating damaged axons. However, the fruit fly model is more user-friendly and allows faster, large-scale genetic analyses.
The fruit fly brain in culture
Although the fruit fly model is used for numerous diseases, until now it has not been possible to study the repair of damaged axons with fruit flies. Indeed, the fruit fly's brain is difficult to access due to the fly's external skeleton, which prevents reproducible, physical manipulations of the living brain. Under the direction of VIB researcher Bassem Hassan, and in collaboration with international experts, Derya Ayaz, Maarten Leyssen and their colleagues have now developed a new technique in which the fruit fly's entire brain is cultured, enabling long-term experimentation (i.e., manipulation and observation) on the living fruit fly brain.
Fruit fly brain as model for studying damaged nerve bundles
The researchers have used this new technique explicitly to develop a fruit fly model for the regeneration of axons after injury. With the aid of micro-dissection, the researchers inflicted injuries on the nerve fibers and then studied them for several days. As is the case for humans, the regeneration of damaged nerve bundles in fruit fly brains is as good as non-existent.
In a next step, the researchers are using this new model to study which molecular processes might be able to promote this regeneration. They have already demonstrated that activation of the JNK signaling pathway positively influences the repair of nerve bundles. JNK activation not only stimulates the growth of the severed nerves but the nerves also grow correctly in the direction of their original target region in the brain.
Perspectives for the future
In the future, this new model can be used to identify new molecules that are involved in the repair of damaged nerve bundles. These molecules will then be candidate molecules for further research with humans, and they can possibly form the basis of new treatments for patients with a nerve injury that has been irreparable up to now.