Brain white matter in aging and disease
The ‚White matter' of the brain is mainly comprised of axons and myelinating glia cells (oligodendrocytes). Since white matter is particularly susceptible to age-dependent pathology, such as atrophy, enhanced inflammation and myelin loss, this line of research focusses on understanding the associated ultrastructural and molecular changes in the composition of senescent myelin. By applying the technique of focussed ion beam/scanning electron microscopy (FIB/SEM) and subsequent 3D modeling of axon/myelin units and associated phagocytotic cells we have unraveled degenerative changes in aging white matter in inevitable detail (Fig. 1).
Moreover, by RNA Sequencing and gel-free mass spectrometry of biochemically purified CNS myelin we have identified several interesting candidate transcripts and proteins that depict profound abundance changes in aged myelin. Consequently, in order to get a better insight whether these changes are cause or effect of white matter aging, we are now in the process of generating and analyzing a series of mouse mutants that allow for the conditional overexpression or inactivation of age-related target genes in myelinating glia cells.
In collaboration with
S. Tenzer, Core Facility for Mass Spectrometry and Protein Biochemistry; Institute for Immunology, Mainz; Olaf Jahn, Proteomics Unit, MPI-NAT, Göttingen; Wiebke Möbius, Electron Microscopy Core Unit, MPI-NAT, Göttingen; H. Werner, Dept. of Neurogenetics, Research group "Neurochemistry", MPI-NAT, Göttingen