Neurobiology of Ageing
One of the most fascinating problems of human biology is the bi-directionality of changes that happen during brain ageing. As we age, we gain knowledge and experience, develop skills, and store memories that define our personality and behaviour. At the same time, the age-associated cognitive advances are marred by decline in neuronal function that may take a particularly dramatic turn in the late stages of human life. How can the wisdom and peril of ageing co-exist and what are the mechanism of these intertwined processes remains largely unknown.
The Schaefer lab studies the neuron-intrinsic and extrinsic mechanisms that govern age-associated brain changes. One of the major focuses of Schaefer's lab is the mechanisms that link peripheral impacts such as infection or inflammation with brain ageing. Infection is an inevitable part of human life that triggers both immune as well as behavioural responses. How these responses are connected is one of the key questions of Schaefer’s research program. The brain has a large population of resident and migratory immune cells that have the potential to affect brain function, both positively and negatively. For many years, studies of age-related neurodegeneration were focused primarily on neuron-intrinsic processes and largely ignored neuronal dependence on immune cells in the brain. Immune cells in the brain are represented by the innate macrophages-like cells in the CNS, the microglia, as well as by traversing peripheral B and T cells. During ageing and infectious diseases, these immune cells can impair brain functions by targeting brain cells in a fashion that resembles autoimmune diseases in the periphery and involves immune cell cytotoxicity. At the same time immune cells may support neuronal function and also “inform” neurons about the processes that take place at the organism “periphery”. How this information can be passed to neurons is not known. Recently we have discovered that microglia can adapt to specific neuronal phenotypes and that alteration in these adaptive processes may lead to aberrant microglial activation and neuronal death. We also found that microglia can control neuronal activity in a neuron-like fashion by using metabolic mediators commonly involved in immunomodulation in the organism periphery.
The overall aim of our research group is to understand the role of the immune-neuron interaction during brain ageing. We are particularly interested in understanding the epigenetic mechanism(s) of microglia adaptation to the neuronal environment and to peripheral impact as well as the mechanism(s) that drive microglia-mediated neuronal pathology. We are keen on defining the immune processes that could be used for treatment and possibly prevention of neurodegenerative diseases in humans.
06/2021 - 05/2027 | European Research Council (Schaefer, Brose, Triller, Oertner MPI), ERC Synergy Grant, Micro-'COPS' - Microglia-control of physiological brain states