Aberrant microglia function as driver of neuroaxonal degeneration in diseases of the white matter

• Applicants: Dr. Caroline Bergner; Dr. Stefan Nessler; Professorin Dr. Christine Stadelmann-Nessler
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 500301720

Brain diseases such as multiple sclerosis and certain hereditary leukodystrophies share specific features such as a predominant involvement of the white matter, important damage to nerve cell processes, in particular axons, and specific forms of activation of "brain tissue macrophages", the so called microglia cells. Microglia cells may even succumb to the disease process, and it is so far unclear whether their lack or their dying induces tissue damage. We want to study here, whether specific functions of microglia cells relate to and are causative for damage to axons and neurons in white matter diseases.In the present work, we strive to identify groups of microglia cells with different functions by analysis of human tissue. By spatial correlation, we will be able to localize specific microglia subgroups in close proximity to damaged neurons or axons. Their functional properties will tell us whether they are candidates for being responsible for the neuronal damage observed. From their gene expression patterns, we will also learn what the damaging insults are that cause their death, dysfunction, and aberrant activation. We will also study human patients by magnetic resonance imaging and will measure molecules in the cerebrospinal fluid and in serum that may serve as indicators of microglia activation and neuronal damage in the brain. This may help to expedite diagnosis and treatment. All in all, the identification of potential „toxic“ functions of microglia shared between several white matter diseases may reveal molecules that may be modulated by novel therapies with the ultimate goal to alleviate neuronal damage.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2395: Local and peripheral drivers of microglial diversity and function