Microvascular and synaptic plasticity in aging

Ageing is related to a dynamic process of ongoing microvascular injury, such as blood-brain barrier disruption, impaired hemodynamics and clearance, i.e., removal of brain protein and metabolite waste products. These processes ultimately lead to synaptic and neural network dysfunction, but could be counterbalanced by continuous microvascular repair, which in turn should be related to maintenance of synaptic and network functioning. We propose, that balance between microvascular injury and repair as well as resistance against microvascular injury in response to physiological stimuli cumulatively fail with increasing age (denoted as “microvascular brain aging”), which feeds into reduced cognitive flexibility and function.
Hence, in close interaction with project B1, we aim to study in rodents (B1) and humans (B2) cortical and hippocampal synaptic function and network connectivity as a function of “microvascular brain ageing”. We specifically focus on the question, how this relationship is influenced by age-related reduced microvascular resistance against physical stress or prolonged recovery. We further particularly investigate how age-related impaired microvascular resistance/recovery and associated declined synaptic and network function can be restored through targeted pharmacological treatment.