PD Dr. med. Björn Spittau
Institute of Anatomy and Cell Biology
University of Freiburg
TGFβ-mediated regulation of microglia functions
Transforming growth factor β1 (TGFβ1) has been shown to be an important endogenous factor to regulate microglia activation states in vitro and in vivo. Our current research aims to elucidate which microglia functions are regulated by TGFβ1 and how this versatile cytokine is mediating its anti-inflammatory effects on microglia. Using primary microglia cultures and transgenic mice with microglia-specific deficiency of TGFβ-signalling, we elucidate the molecular mechnisms as well as the importance of TGFβ1-mediated effects on microglia in vitro and in vivo.
Microglia functions during development, maintenance and aging of the nigrostriatal system
Although microglia have been initially described as lesion-associated cells of the central nervous system, recent reports have changed the view of the scientific community and microglia are now considered as important cells supporting neurodevelopment and maintenance of neuronal circuits. We are focused on the nigrostriatal system which is composed of midbrain dopaminergic (mDA) neurons, their projections to the basal ganglia as well as the basal ganglia itself. This system is involved in the control of motor functions and degeneration of mDA neurons is one of the hallmarks of Parkinson´s disease (PD). We are currently addressing the role of microglia during the postnatal maturation of the nigrostriatal system, where microglia are highly active and seem to be involved in clearance of apoptotic cells and shaping of synaptic connections. Moreover, we analyse the age-dependent changes in microglia functions and activation states and the resulting consequences for age-dependent loss of mDA neurons.
Microglia activation patterns and their role during degeneration of mDA neurons in PD model
Parkinson´s disease is the second most common neurodegenerative disease and is characterised by typical motor symptoms such as bradykinesia, tremor and rigidity. The symptoms are caused by degeneration of mDA neurons and a subsequent decrease in dopamine levels in the basal ganglia. In most of the cases, the reasons for this progressive degeneration of mDA neurons is not clear. However, a strong neuroinflammatory response mediated by microglia seems to be a common hallmark of almost all PD cases. Using mouse models for PD, we are analysing the temporal and spatial activation patterns of microglia in order to understand to which extent microglia contribute to degeneration of mDA neurons during the course of PD.